. _:b419251059 . _:b419250667 . . . . _:b419250356 . . . _:b419250816 . _:b419250755 . . _:b419251030 . . _:b419250481 . _:b419250425 . . . . . _:b419250181 . _:b419250631 . _:b419250440 . _:b419251093 . . . . . . . _:b419250253 . . _:b419250352 . . . _:b419250556 . _:b419250162 . . . _:b419250158 . . _:b419251004 . _:b419250917 . . . . _:b419251137 . _:b419250715 . _:b419251145 . _:b419250890 . _:b419250184 . . . _:b419250065 "26"^^ . _:b419250067 "19"^^ . _:b419250063 "37"^^ . _:b419250478 . _:b419250066 "21"^^ . _:b419250064 "29"^^ . _:b419250355 . _:b419250061 "53"^^ . _:b419250068 "18"^^ . _:b419250218 . _:b419250069 "16"^^ . . _:b419250070 "16"^^ . _:b419250062 "49"^^ . _:b419250071 "15"^^ . . _:b419250072 "14"^^ . . . _:b419250079 "13"^^ . _:b419250073 "14"^^ . . _:b419250078 "13"^^ . . _:b419250077 "13"^^ . _:b419250076 "13"^^ . _:b419250075 "13"^^ . _:b419250381 . _:b419250074 "13"^^ . . . _:b419250379 . _:b419250207 . _:b419250087 "10"^^ . _:b419250086 "10"^^ . _:b419250085 "11"^^ . . . _:b419250084 "11"^^ . _:b419250083 "11"^^ . _:b419250904 . _:b419250082 "11"^^ . _:b419250901 . _:b419250081 "12"^^ . _:b419250395 . . . _:b419250080 "12"^^ . . _:b419250094 "8"^^ . . . _:b419250095 "8"^^ . . _:b419250509 . _:b419250092 "9"^^ . _:b419250880 . _:b6461039 . _:b419250093 "8"^^ . _:b419250432 . . _:b419250090 "9"^^ . . _:b419250091 "9"^^ . . _:b419250457 . _:b419250088 "10"^^ . _:b419250089 "9"^^ . _:b419250774 . _:b419250102 "7"^^ . _:b419250292 . _:b419250103 "7"^^ . _:b419250391 . _:b419250983 . _:b419250100 "8"^^ . _:b419250101 "7"^^ . _:b419250098 "8"^^ . _:b419250128 . _:b419250415 . _:b419250099 "8"^^ . . _:b419250096 "8"^^ . _:b419250603 . . _:b419250097 "8"^^ . _:b419250849 . _:b419250110 "7"^^ . _:b419250111 "7"^^ . _:b419250464 . _:b419250108 "7"^^ . _:b419250511 . _:b419250109 "7"^^ . _:b419251013 . _:b419250106 "7"^^ . _:b419250107 "7"^^ . _:b419250104 "7"^^ . _:b419250105 "7"^^ . . . _:b419250118 "6"^^ . . . . _:b419250119 "6"^^ . _:b419250116 "6"^^ . . _:b6461036 "Mitochondrial dysfunction decreases fat oxidation, leading to accumulation of these lipids, which decrease insulin sensitivity (>>41<<,42). Since resveratrol increases mitochondrial function (7), we measured the DAG and ceramide levels in resveratrol-treated skeletal muscle. As shown in Fig. 4D and E, resveratrol decreased DAG and ceramide levels in wild-type mice but" . . . _:b419250117 "6"^^ . _:b419250114 "6"^^ . . _:b419250190 . _:b419250115 "6"^^ . _:b419250135 . _:b419250112 "7"^^ . _:b419250867 . _:b419250113 "7"^^ . _:b419250126 "6"^^ . . _:b419250127 "6"^^ . _:b419250345 . _:b419250124 "6"^^ . _:b419251213 . _:b419250125 "6"^^ . _:b419250122 "6"^^ . . _:b419250123 "6"^^ . _:b419250120 "6"^^ . _:b419250746 . _:b419250320 . _:b419250121 "6"^^ . . . . _:b419250133 "5"^^ . . . _:b419250132 "5"^^ . _:b419250180 . _:b419250135 "5"^^ . _:b419250328 . _:b419250134 "5"^^ . _:b419250130 "6"^^ . _:b419250131 "6"^^ . _:b419250128 "6"^^ . _:b419250129 "6"^^ . _:b419250828 . _:b419250498 . _:b419250809 . _:b419250803 . _:b419250141 "5"^^ . _:b419250140 "5"^^ . . . _:b419250143 "5"^^ . _:b419250646 . _:b419250142 "5"^^ . _:b419250555 . _:b419250121 . _:b419250137 "5"^^ . _:b419250136 "5"^^ . _:b6461023 . . _:b419250139 "5"^^ . . _:b419250138 "5"^^ . . _:b419250149 "5"^^ . . _:b419250148 "5"^^ . _:b419251033 . _:b419250151 "5"^^ . _:b419250150 "5"^^ . _:b419251122 . _:b419251187 . _:b419250145 "5"^^ . _:b419250543 . _:b419250144 "5"^^ . _:b419250147 "5"^^ . . _:b419250835 . _:b419250146 "5"^^ . _:b419250157 "5"^^ . _:b419250769 . . _:b419250156 "5"^^ . . _:b419250159 "5"^^ . _:b419250398 . _:b419250158 "5"^^ . _:b419250153 "5"^^ . _:b419251203 . _:b6461077 "Reactive oxygen species (ROS) levels were determined in muscle extracts using the ROS-sensitive fluorescent dye dichlorodihydrofluorescein (DCF), as previously described (>>29<<,30). Briefly, oxidation-insensitive dye (carboxy-DCFDA) was used as a control to ensure that changes in the fluorescence seen with the oxidation-sensitive dye (H2DCFDA) were due to changes in ROS production." . _:b419250152 "5"^^ . _:b419251193 . _:b419250650 . . _:b419250155 "5"^^ . . _:b419250154 "5"^^ . _:b419250165 "5"^^ . . _:b419250164 "5"^^ . _:b419250167 "5"^^ . _:b6461058 "One possible explanation for the reduced fat mass in the knockin mice (36) is that expression of the Sirt1 transgene from the \u03B2-actin locus impaired adipocyte differentiation during development (>>49<<). Therefore, the Sirt1 knockin model (36) cannot distinguish between a direct effect of Sirt1 and an indirect one caused by reduced fat." . _:b419250166 "5"^^ . _:b419250681 . _:b419250161 "5"^^ . _:b419250160 "5"^^ . _:b419250163 "5"^^ . _:b419250684 . _:b419250162 "5"^^ . _:b419250173 "4"^^ . . . . _:b419250172 "4"^^ . _:b419250333 . _:b419251052 . _:b419250175 "4"^^ . _:b419251048 . _:b419250174 "4"^^ . _:b419250745 . _:b419250169 "4"^^ . _:b6461037 "Mitochondrial dysfunction decreases fat oxidation, leading to accumulation of these lipids, which decrease insulin sensitivity (41,>>42<<). Since resveratrol increases mitochondrial function (7), we measured the DAG and ceramide levels in resveratrol-treated skeletal muscle. As shown in Fig. 4D and E, resveratrol decreased DAG and ceramide levels in wild-type mice but not" . . _:b419250168 "5"^^ . _:b419250280 . _:b419250171 "4"^^ . _:b419250711 . _:b419250170 "4"^^ . . . . . . _:b419250237 . . . . . _:b419251148 . _:b419250389 . . _:b419250144 . . . _:b419250800 . _:b419250289 . _:b419250294 . _:b419251121 . _:b419250344 . . . . . _:b419250455 . . . _:b419251016 . . . _:b419250799 . _:b419250273 . . _:b419250697 . . . . _:b419250261 . . . _:b419250073 . _:b419250421 . _:b419250525 . . . _:b419250193 . . _:b419250808 . _:b419250450 . . _:b419250169 . . _:b419250560 . . _:b419250956 . . . _:b6461029 "Sirt1 overexpression (35\u201337), AMPK activation (21,22,>>38<<), and resveratrol treatment (5,7) all improve glucose tolerance and insulin sensitivity." . _:b419250709 . _:b419250220 . _:b419250676 . . _:b419250830 . . _:b419250448 . . _:b419250299 . _:b419250733 . _:b419250896 . . _:b419250110 . _:b419250170 . _:b419250208 . _:b419250412 . . . _:b6461065 "Whether it is the direct target of resveratrol or not, it appears that Sirt1 can also function upstream of AMPK in HepG2 hepatocytes and HEK293T cell line (>>26<<,27). Since Sirt1 is not required for resveratrol-mediated activation of AMPK activation in mefs (Fig. 6A), it is possible that Sirt1 is upstream of AMPK only in certain cell types." . _:b419250078 . _:b419251164 . . . . _:b419250438 . _:b419250606 . _:b419250853 . . . . _:b6461046 . . . . _:b419250282 . . _:b419250633 . . _:b419250976 . . _:b419251066 . _:b419250915 . _:b419250909 . _:b419251003 . . _:b419250167 . _:b419250586 . . _:b419250554 . . _:b419251105 . _:b419250251 . . . . . . _:b419250943 . . _:b419250813 . . _:b419250612 . . _:b419251106 . . . _:b419250089 . _:b419251151 . _:b419250934 . . _:b419250154 . . . _:b419250802 . . _:b419250598 . _:b419250094 . . . . _:b419250222 . . . . _:b419250559 . _:b419250295 . . _:b419250101 . _:b419250315 . . _:b419250467 . . . _:b419250782 . . . _:b419251119 . _:b419251115 . . _:b419250602 . . _:b419250186 . _:b419250963 . . _:b419250435 . _:b419250373 . _:b6461045 "A previous report (>>7<<) showed that resveratrol did not induce PGC-1\u03B1 transcription in Sirt1\u2212/\u2212 mefs and concluded that Sirt1 is essential for resveratrol-induced transcription of PGC-1\u03B1." . . _:b419250998 . _:b419251022 . _:b419250370 . _:b419250971 . . _:b419250257 . . _:b419250084 . _:b419250451 . _:b419251045 . . _:b419250540 . . _:b6461067 . . _:b419251205 . _:b419251204 . _:b419251207 . _:b419251206 . . . _:b419251201 . . . _:b419251200 . . _:b6461056 . _:b419251203 . . _:b419251202 . . _:b419251213 . _:b419251212 . . _:b419251215 . . _:b419251214 . _:b419251209 . . _:b419251071 . _:b419251208 . _:b419250815 . _:b419250269 . . _:b419251211 . _:b419251210 . _:b6461044 "PGC-1\u03B1 is a coactivator for its own transcription (>>46<<), and, as a result, deacetylation of PGC-1\u03B1 by Sirt1 should increase its ability to positively regulate PGC-1\u03B1 transcription." . _:b419251217 . _:b419251216 . . _:b419250319 . _:b419250936 . . . . _:b6461076 . . _:b419250908 . . . _:b419250592 . _:b419250757 . . . _:b419250750 . _:b419250891 . _:b419250804 . . . _:b419250245 . _:b419250988 . _:b419250201 . _:b419250531 . _:b419251181 . _:b419251046 . . . _:b419250508 . _:b419250338 . _:b419250781 . . _:b419251064 . . . . . _:b419251021 . _:b419250682 . _:b419250434 . _:b419251202 . . . . _:b419250770 . _:b419250510 . . . . _:b419250439 . _:b419250877 . _:b419250688 . _:b419250263 . _:b419251060 . . . _:b419250655 . . . . _:b419251086 . _:b419250671 . . _:b419250441 . _:b6461064 . _:b419250079 . _:b419250076 . . _:b419250250 . . _:b419251129 . . . . . . . . _:b419250752 . _:b419251075 . _:b419251149 . . _:b419250613 . _:b419250372 . _:b419251138 . . . . _:b419250124 . _:b419250143 . _:b6461070 "We do not have a clear explanation for this, but one possibility is that the antiadipogenic function of Sirt1 (>>49<<) is being driven by the resveratrol-AMPK\u03B11-Sirt1 pathway in AMPK\u03B12\u2212/\u2212 mice." . _:b419250780 . . _:b419250873 . . _:b419250114 . _:b419250350 . . _:b419250102 . _:b419250742 . _:b419251130 . _:b419250789 . _:b419250098 . . . _:b419250629 . . . . _:b419250949 . . _:b419250296 . . _:b419250486 . . _:b419250812 . . _:b419250593 . _:b419251088 . _:b419250387 . . . . . _:b419250662 . . . _:b419250749 . . . _:b419250844 . _:b419250500 . _:b6461043 "Since AMPK activity increases the NAD-to-NADH ratio and Sirt1 activity (>>45<<), we measured the NAD-to-NADH ratio in C2C12 myotubes treated with resveratrol for 6 and 16 h." . _:b419250347 . _:b419250477 . _:b419250692 . . _:b419250394 . _:b419250825 . . _:b419250145 . . _:b419250416 . _:b419250751 . . _:b419251186 . . _:b419250264 . _:b6461035 "Insulin-resistant tissues are often associated with elevated levels of intramyocellular lipids such as diacylglyceride (DAG) and ceramide (>>41<<). Mitochondrial dysfunction decreases fat oxidation, leading to accumulation of these lipids, which decrease insulin sensitivity (41,42)." . _:b6461038 . _:b419251185 . . _:b419250495 . . . _:b419250414 . _:b419250203 . _:b419250811 . . _:b419250072 . _:b6461031 . _:b419250672 . _:b419251005 . _:b419250463 . _:b419250549 . _:b419250886 . _:b419250547 . _:b6461042 . _:b6461045 . . . . . _:b419250658 . _:b419250082 . _:b419250230 . _:b419250627 . . . . . . . _:b419250610 . _:b419250924 . _:b419250942 . . . _:b419250153 . _:b419251051 . _:b419250422 . . _:b419250325 . . _:b6461049 . _:b419251144 . . _:b6461022 . . . _:b419250727 . . _:b419250553 . _:b419250793 . . . _:b419250533 . . _:b419250164 . . . _:b419250288 . . _:b419250132 . . _:b419250129 . . . _:b419250077 . . _:b6461026 . . . . _:b6461048 . _:b6461051 . . . _:b6461046 "Consistent with previous reports (>>47<<), \u2212Sirt1 mefs had higher AMPK activity than +Sirt1 mefs (Fig." . _:b419250952 . _:b419250215 . _:b6461054 . . _:b419251215 . _:b419250386 . . . _:b419250400 . _:b419250210 . . . . . . _:b419251198 . . . _:b419250675 . _:b419250694 . . _:b419250949 . . . _:b419250948 . _:b419250260 . _:b419251120 . _:b419250951 . _:b419250950 . . _:b419251053 . _:b419250945 . _:b419250944 . _:b419250532 . . _:b419250947 . _:b419250946 . _:b419250202 . _:b419250957 . _:b419250956 . _:b419250139 . _:b419251077 . _:b419250959 . _:b419251197 . _:b419250958 . . . _:b419250953 . _:b419250952 . _:b419250548 . _:b419250955 . _:b419250957 . _:b419250954 . . _:b6461061 "Resveratrol has been reported to affect the activities of many enzymes (11) including AMPK (>>12<<). To evaluate the possibility that the effects of resveratrol are mediated by AMPK, we studied the effects of resveratrol in mice deficient in AMPK\u03B11 or -\u03B12." . . _:b419250965 . . _:b419250964 . _:b419250967 . _:b419250966 . _:b419250961 . . _:b419250960 . . _:b419250963 . _:b419250962 . _:b419250973 . . _:b419250115 . _:b419250702 . . _:b419250972 . . _:b419250975 . . _:b419250974 . _:b419250969 . . _:b419250968 . _:b419251015 . . _:b419250971 . . _:b419250970 . . _:b419250722 . _:b419250981 . _:b6461066 "Whether it is the direct target of resveratrol or not, it appears that Sirt1 can also function upstream of AMPK in HepG2 hepatocytes and HEK293T cell line (26,>>27<<). Since Sirt1 is not required for resveratrol-mediated activation of AMPK activation in mefs (Fig. 6A), it is possible that Sirt1 is upstream of AMPK only in certain cell types." . _:b419250980 . _:b419250990 . _:b419250983 . . . _:b419250982 . _:b419250977 . . . . _:b419251092 . _:b419250976 . _:b419250256 . _:b419250479 . _:b419250159 . _:b419250979 . . _:b419250978 . _:b419250622 . _:b419250989 . _:b419250988 . . _:b419250991 . _:b419250993 . _:b419250990 . _:b419250163 . _:b419250985 . . _:b419250768 . _:b419250984 . _:b419250088 . _:b419250987 . _:b419250221 . _:b419250986 . . _:b419250997 . _:b419250175 . _:b419250903 . _:b6461025 . _:b419250996 . _:b419250999 . _:b419250673 . . . _:b419250998 . _:b419251117 . . . _:b419250993 . _:b419250992 . . _:b419250666 . _:b419250995 . . _:b419251190 . _:b419250994 . _:b419251005 . . _:b419251004 . _:b419251007 . _:b419251006 . _:b6461078 "Reactive oxygen species (ROS) levels were determined in muscle extracts using the ROS-sensitive fluorescent dye dichlorodihydrofluorescein (DCF), as previously described (29,>>30<<). Briefly, oxidation-insensitive dye (carboxy-DCFDA) was used as a control to ensure that changes in the fluorescence seen with the oxidation-sensitive dye (H2DCFDA) were due to changes in ROS production." . _:b419251001 . . _:b6461037 . _:b419251000 . . _:b419251003 . _:b419251002 . _:b419251013 . . _:b419251201 . _:b419250913 . . _:b419251012 . . _:b419251015 . _:b419251014 . . _:b419251009 . _:b419251008 . . _:b419250316 . _:b419250820 . . _:b419251011 . _:b419250097 . _:b419251010 . _:b419251021 . _:b419250485 . . . _:b419251020 . _:b6461080 . _:b419251023 . _:b419250577 . _:b419250247 . _:b419251022 . _:b419251017 . _:b419250142 . _:b419251016 . _:b419251179 . _:b419250704 . . _:b419251019 . . _:b419251018 . _:b419251029 . . _:b419251028 . _:b419250132 . _:b419250133 . _:b419250134 . _:b419250135 . _:b419251031 . _:b419250128 . _:b419250129 . _:b419250130 . _:b419250131 . _:b419251030 . _:b419250140 . _:b419251124 . _:b419250141 . _:b419250142 . _:b419250143 . _:b419251025 . _:b419250136 . _:b419250137 . _:b419250941 . _:b419250138 . _:b419250139 . _:b419251024 . _:b419250116 . _:b419250117 . _:b419250118 . . _:b419250119 . _:b419251027 . _:b419250112 . _:b419250113 . _:b419250114 . _:b6461048 "One target for treating metabolic disorders is Sirt1 (>>8<<), an NAD+-dependent protein deacetylase (48)." . _:b419250115 . _:b419251026 . _:b419250124 . _:b419250125 . _:b419250126 . _:b419250866 . _:b419250127 . _:b419251037 . _:b419250120 . _:b419250121 . _:b419250122 . . _:b419250123 . _:b419251036 . _:b419250164 . _:b419250165 . _:b419250166 . _:b419250167 . _:b419251039 . _:b419250160 . _:b419250161 . _:b419250162 . _:b419250382 . _:b419250163 . _:b419251038 . _:b419250172 . _:b419251141 . _:b419250173 . _:b419250174 . _:b419250175 . _:b419251033 . _:b419250168 . _:b419250169 . . _:b419250170 . _:b419250171 . _:b419251032 . _:b419250148 . _:b419250149 . _:b419250150 . . _:b419250151 . _:b419251035 . _:b419250144 . _:b419250145 . _:b419250146 . _:b419250147 . . _:b419251034 . . _:b419250156 . _:b419250609 . _:b419250157 . _:b419250158 . _:b419250159 . _:b419251045 . _:b419250152 . _:b6461053 . _:b419250153 . _:b419250154 . _:b419250155 . _:b419251044 . _:b419250068 . _:b419250069 . _:b419250070 . _:b419250071 . _:b419251047 . _:b419250064 . _:b419250777 . _:b419250065 . _:b419250066 . _:b419250067 . _:b419251046 . _:b419250076 . _:b419250077 . _:b419250078 . _:b419250079 . _:b419251041 . _:b419250072 . _:b419250073 . _:b419250875 . _:b419250074 . _:b419250075 . _:b419251040 . . _:b419251043 . . _:b419251042 . _:b419250061 . . _:b419250348 . _:b419250062 . _:b419250063 . _:b419251053 . . _:b419251052 . _:b419250100 . _:b419250101 . _:b419250102 . _:b419250103 . _:b419251055 . _:b419250096 . _:b419250097 . _:b419250098 . _:b419250099 . _:b419251054 . _:b419250108 . _:b419250109 . _:b419250110 . _:b419250111 . _:b419251049 . _:b419250104 . _:b419250604 . _:b419250105 . _:b419250106 . _:b419250107 . _:b419251048 . _:b419250084 . _:b419250085 . . _:b419250086 . _:b419250087 . _:b419251051 . _:b419250080 . _:b419250081 . _:b419250082 . . _:b419250083 . _:b419250616 . _:b6461051 "In Sirt1 knockin mice (>>36<<), the Sirt1 transgene, which was expressed from the \u03B2-actin locus, is overexpressed in fat but not in muscle or liver, key organs affected in metabolic disorders." . _:b419250092 . _:b419251050 . _:b419250093 . _:b419250693 . _:b419250094 . _:b419250095 . . _:b419251061 . _:b419250088 . _:b419250089 . _:b419250090 . _:b419250091 . _:b419251060 . . _:b419250720 . _:b419251063 . _:b419251073 . _:b6461065 . _:b419251062 . _:b419251057 . _:b419250640 . _:b419251056 . _:b419250617 . . _:b419251059 . . _:b419250314 . . _:b419251058 . _:b419251069 . _:b419251068 . . _:b419251071 . _:b419251070 . _:b6461026 . _:b419251065 . _:b419251064 . _:b419251067 . _:b419250177 . _:b419251167 . _:b419251066 . _:b419251069 . _:b419251077 . _:b419251076 . _:b419250529 . _:b419251079 . _:b6461057 . _:b419251078 . _:b419251073 . _:b419250487 . _:b6461059 . _:b419251072 . _:b419250966 . _:b419250383 . _:b419251075 . _:b6461029 . _:b419251074 . . _:b419251085 . . _:b419250607 . . _:b419251084 . . _:b419251087 . _:b419251086 . _:b419251081 . _:b419251080 . _:b419251098 . _:b419251162 . _:b419251083 . . _:b419251082 . _:b419250349 . _:b419251093 . . _:b419251092 . _:b419250664 . _:b419251095 . _:b419250939 . . _:b419251094 . . . _:b419251089 . . . _:b419251088 . . _:b419250183 . . _:b419251091 . . . _:b419251090 . _:b419251205 "2"^^ . _:b419251101 . _:b419251204 "2"^^ . _:b419251100 . _:b419251207 "2"^^ . _:b419251103 . . _:b419251206 "2"^^ . . . _:b419251102 . _:b419251201 "2"^^ . _:b6461040 . _:b419251097 . _:b419250535 . _:b419251200 "2"^^ . _:b419251096 . _:b419251203 "2"^^ . _:b419251099 . _:b419251202 "2"^^ . . . _:b419250304 . _:b419251098 . . _:b419251213 "2"^^ . _:b419250241 . . _:b419251109 . _:b419251212 "2"^^ . _:b419251008 . _:b419251108 . _:b6461069 "However, it is also likely that the glycogen content in skeletal muscle, which is known to be increased by AMPK activity (>>34<<), also plays a role in resveratrol-induced physical endurance." . _:b419251215 "2"^^ . _:b419250585 . _:b419251111 . _:b419251214 "2"^^ . _:b419250710 . _:b419251110 . _:b419251209 "2"^^ . _:b419250852 . _:b419251105 . _:b419251208 "2"^^ . . _:b6461052 "More recently, transgenic mice in which the Sirt1 transgene is expressed from its own promoter have been reported by two independent groups (>>35<<,37). These transgenic mice, which have a more physiological expression pattern of the Sirt1 transgene than the knockin mice (36), are more insulin sensitive partly due to increased adiponectin levels and decreased hepatic steatosis." . _:b419251104 . _:b419251211 "2"^^ . . . _:b419251107 . . _:b419251210 "2"^^ . _:b419251106 . . _:b419250978 . . _:b419251117 . _:b419251116 . . . _:b419251119 . _:b419251118 . _:b419250583 . _:b419251217 "2"^^ . _:b419251113 . _:b419251216 "2"^^ . _:b419251112 . _:b419250234 . _:b419251115 . _:b419251114 . . _:b419250771 . _:b419251125 . . _:b419251124 . . _:b419250341 . _:b419251127 . . _:b419250621 . _:b419251126 . _:b419251121 . _:b419250520 . _:b419251120 . _:b419251123 . _:b419250689 . _:b419251054 . _:b419251122 . . _:b419250335 . . _:b419251133 . _:b419250837 . _:b419251132 . . _:b419251135 . . _:b419251134 . . . _:b419251129 . _:b419251036 . _:b419251128 . _:b419250086 . _:b419250233 . _:b419250731 . _:b419251131 . _:b419251130 . _:b419250824 . _:b419250762 . _:b419251141 . _:b419251140 . _:b419251143 . _:b419251142 . _:b419251029 . . _:b419250123 . _:b419251137 . _:b6461023 "Prolonged activation of AMPK increases Glut4 expression (>>33<<). To determine whether increased expression of Glut4 expression was involved in the resveratrol-mediated improvement of physical endurance, we measured Glut4 mRNA levels in skeletal muscle." . . _:b419251136 . _:b419251139 . _:b419251138 . _:b419250845 . _:b419251149 . _:b419250596 . _:b419251148 . _:b419251151 . . _:b419251180 . . _:b419250505 . _:b419251150 . _:b419251145 . _:b419250644 . _:b419250567 . _:b419251144 . . . . _:b419251147 . _:b419251146 . _:b419251157 . . _:b419251156 . _:b419250946 . _:b419251159 . _:b419251158 . _:b419250605 . _:b419250973 . _:b419250625 . _:b419251153 . _:b419251152 . . _:b419251155 . . _:b419251154 . _:b419250767 . _:b419251165 . _:b419250182 . _:b419251164 . . . _:b419251167 . _:b419251166 . . _:b419251161 . _:b419251191 . _:b419251160 . _:b419251163 . _:b419251178 . _:b419251162 . _:b419251173 . _:b419250312 . _:b419251172 . . . . _:b419251175 . _:b6461075 "AMPK\u03B12\u2212/\u2212 (22) and AMPK\u03B11\u2212/\u2212 (>>28<<) mice were backcrossed to C57BL/6J for at least six generations before this study." . _:b419251174 . _:b419251169 . _:b419251168 . _:b419250916 . _:b419250660 . _:b419251171 . _:b419250910 . _:b419251024 . _:b419251170 . . . _:b419250685 . _:b419251181 . . _:b419251180 . _:b419250878 . _:b419251183 . _:b419251182 . _:b419251177 . _:b419251176 . . _:b419251070 . . _:b419250986 . _:b419251179 . _:b419251178 . _:b419251189 . . _:b419251188 . _:b419251191 . . _:b419251190 . . _:b419251185 . . _:b419251184 . _:b419250272 . _:b419250514 . _:b419251187 . _:b419250657 . "10.2337%2Fdb09-0482" . _:b419250883 . _:b419251186 . _:b419251197 . _:b6461039 "Adiponectin, a cytokine that is produced by fat and is decreased in obese and diabetic subjects (>>43<<), increases insulin sensitivity by activating AMPK (38)." . _:b419251196 . _:b419251199 . _:b419251198 . _:b419251193 . . _:b419251192 . _:b6461074 "AMPK\u03B12\u2212/\u2212 (>>22<<) and AMPK\u03B11\u2212/\u2212 (28) mice were backcrossed to C57BL/6J for at least six generations before this study." . _:b419251195 . . _:b419251194 . _:b419250632 . _:b419250368 . _:b419250693 . _:b419250692 . . _:b419250695 . _:b419250229 . . _:b419250694 . . _:b419250476 . _:b419250689 . _:b419250469 . _:b419250688 . . _:b419250691 . _:b419250690 . . _:b419250092 . _:b419250701 . _:b419250700 . _:b419251127 . _:b419250703 . _:b419250702 . . _:b419250291 . _:b419250697 . _:b419250346 . _:b419250696 . . _:b419250699 . _:b419250698 . . _:b419250709 . _:b6461075 . _:b419250061 . _:b419250708 . _:b419250711 . _:b419250063 . _:b419251038 . . _:b419250259 . . _:b419250927 . _:b419250710 . _:b419250062 . _:b419250705 . . . _:b419250704 . _:b419250707 . _:b419250490 . _:b419250147 . _:b419250706 . . _:b419250717 . _:b419250069 . . . _:b419250716 . _:b419250357 . _:b419250068 . _:b419250719 . _:b419250445 . _:b419250071 . _:b419250718 . _:b419250070 . _:b419250713 . _:b419250065 . _:b419250712 . . _:b419251160 . _:b419250064 . . _:b419250715 . _:b419250846 . _:b419250067 . . _:b419250714 . _:b419250066 . _:b419250725 . . _:b419250077 . _:b419250724 . . _:b419250076 . _:b6461034 "Insulin-resistant states are associated with increased production of ROS, and reduction of ROS with antioxidants improves insulin sensitivity (39,>>40<<). Since resveratrol is thought to have antioxidant properties, it is possible that some insulin sensitizing of resveratrol effect may be related to its antioxidant effect." . _:b419250727 . _:b419251014 . _:b419250079 . _:b419250726 . _:b419250078 . _:b419250721 . . _:b419250073 . . _:b419250720 . . _:b419250072 . _:b419250723 . _:b419250075 . . _:b419250722 . _:b419250074 . _:b419250935 . . _:b419250733 . _:b419250085 . _:b6461068 . _:b419250732 . _:b419250084 . . _:b419250211 . _:b419250735 . . _:b419250087 . _:b419250734 . _:b419250086 . _:b419250729 . _:b419250081 . _:b419250728 . _:b419250721 . _:b419250080 . . _:b419250731 . . _:b419250083 . _:b419250730 . _:b419251057 . _:b419250082 . _:b419250332 . _:b419250741 . _:b419250369 . _:b419250093 . _:b419250740 . _:b419250892 . _:b419250318 . _:b419250092 . _:b419250743 . _:b419250095 . _:b419250742 . . _:b419250094 . _:b419250737 . _:b419250089 . _:b419250736 . _:b419250659 . _:b419250088 . _:b419250739 . _:b419250091 . _:b419250738 . _:b419250090 . . _:b419250749 . _:b419250101 . _:b419250748 . . _:b419250100 . . . _:b419250751 . _:b419250103 . . _:b419250750 . . _:b419250102 . . _:b419250995 . _:b419250745 . _:b419250097 . _:b419250744 . _:b419250096 . . _:b419250747 . _:b419250099 . _:b419250746 . _:b419250098 . _:b419250757 . _:b419250109 . _:b419250417 . _:b419250756 . _:b419250108 . _:b6461076 "and fed a high-fat diet (40% calories from fat; Bio-serv) or a high-fat diet supplemented with resveratrol (400 mg \u00B7 kg\u22121 \u00B7 day\u22121; Orchid Chemicals and Pharmaceuticals) for 12 weeks as previously described (>>7<<). All experiments were approved by the National Heart, Lung, and Blood Institute Animal Care and Use Committee." . _:b419250759 . _:b419250111 . _:b419250758 . _:b419250683 . . . _:b419250110 . _:b419250753 . . . _:b419250105 . . _:b419250752 . _:b419250104 . _:b419250497 . _:b419250755 . _:b419250107 . . _:b419250165 . _:b419250754 . _:b419250573 . _:b419250106 . _:b419250765 . _:b419250117 . _:b419250764 . . _:b419250116 . _:b419250767 . . _:b419250413 . _:b419250119 . _:b419250116 . _:b419250766 . _:b6461072 "One possible explanation is that in addition to the AMPK\u03B12 activity, a crosstalk between the skeletal muscle and either the nervous system or fat, where the AMPK\u03B11 isoform is predominant (>>17<<), is required for resveratrol-induced mitochondrial biogenesis or reduction of ROS in skeletal muscle." . _:b419250118 . _:b419250761 . _:b419250113 . _:b419250760 . _:b419250847 . _:b419250112 . _:b419250763 . _:b419250115 . _:b419250762 . _:b419250114 . _:b419250773 . _:b419251027 . _:b419250125 . . _:b419250772 . _:b419250124 . _:b419250775 . _:b419250127 . . _:b419250774 . _:b419250492 . _:b419250126 . _:b419250769 . . _:b419250121 . . _:b419250651 . _:b419250768 . _:b419250120 . . _:b419250771 . _:b419250123 . _:b419250770 . . _:b419250122 . _:b419250781 . _:b419250133 . _:b419250780 . . _:b419250695 . _:b419251196 . _:b419250132 . . _:b419250783 . _:b419250070 . _:b419250135 . _:b419250782 . _:b419250134 . . _:b419250777 . _:b419250538 . _:b419250129 . _:b419250776 . _:b419250724 . _:b419250128 . _:b419250779 . _:b419250131 . _:b419250778 . _:b419250130 . _:b419250789 . _:b419250141 . _:b419250788 . _:b419251114 . _:b419250140 . _:b419250791 . . _:b419250143 . _:b419250790 . _:b419251006 . . _:b419250142 . _:b419250785 . _:b419250137 . _:b419250784 . _:b419250708 . . _:b419251103 . _:b419250136 . _:b419250945 . _:b419250323 . _:b419250778 . _:b419250787 . _:b419250139 . _:b419250786 . _:b419250138 . _:b419250840 . _:b419250797 . _:b419250149 . _:b419250796 . _:b419250148 . _:b419250799 . _:b419250151 . _:b419250798 . _:b419250150 . _:b419250155 . _:b419250793 . _:b419250145 . _:b419250792 . . _:b419250144 . _:b419250473 . . _:b419250795 . _:b419251058 . . _:b419250147 . _:b419251040 . _:b419250794 . . _:b419250146 . _:b419250507 . _:b419250805 . _:b419251211 . _:b419250157 . . _:b419250804 . _:b419250156 . . _:b419250807 . _:b419250159 . _:b419250975 . _:b419250806 . _:b419250158 . _:b419250801 . _:b419250153 . _:b419250800 . _:b419250152 . _:b419250595 . _:b419251099 . _:b419250093 . _:b419250803 . _:b419250155 . _:b419251068 . _:b419250802 . _:b419250324 . _:b419250154 . _:b419250813 . _:b419250165 . _:b419250812 . _:b419250164 . . _:b419250815 . _:b419250167 . _:b419250814 . _:b419250166 . _:b419250987 . _:b419250809 . . . _:b419250161 . _:b419250808 . _:b419250160 . _:b419250811 . _:b419250163 . _:b419250065 . _:b419250810 . _:b419250162 . _:b419251001 . _:b419250821 . . _:b419250470 . _:b419250173 . _:b419250305 . _:b419250820 . _:b419251161 . _:b419250172 . _:b419250823 . _:b419250175 . . _:b419250822 . _:b419250174 . _:b419250817 . _:b419250366 . _:b419250169 . _:b419250816 . _:b419250168 . _:b419250194 . _:b419250819 . _:b419250171 . _:b419250818 . _:b419250170 . . _:b419250829 . _:b419250572 . _:b419250828 . _:b419250502 . _:b419250831 . _:b419250830 . _:b419250825 . _:b419250824 . _:b419250827 . _:b419250826 . _:b419250837 . . _:b419251002 . _:b419250836 . _:b419250839 . . _:b419250838 . . _:b419250833 . _:b419250832 . _:b419250835 . _:b419250967 . _:b419250834 . _:b419250845 . _:b419250844 . _:b419250734 . _:b419250847 . _:b419250846 . _:b419251020 . _:b419250841 . _:b419250933 . _:b419250840 . _:b419250397 . _:b419250843 . . _:b419250842 . _:b419250409 . _:b419251089 . _:b419250853 . . _:b419250852 . . . _:b419250855 . _:b419250854 . _:b419251143 . _:b419250849 . _:b419250706 . . . _:b419250848 . _:b419251019 . . _:b419250851 . . _:b419250850 . . . _:b419250861 . _:b419250843 . . _:b419250860 . _:b419250204 . _:b419250863 . . _:b419251139 . _:b419250862 . . _:b419250436 . _:b419250857 . _:b419250931 . . _:b419250856 . _:b419250859 . _:b419250858 . _:b419250869 . _:b419250868 . . _:b419250871 . _:b419250728 . _:b419250337 . _:b419250870 . . _:b419250865 . _:b419250864 . . _:b419250867 . _:b419250866 . _:b419250877 . _:b419250561 . _:b419250876 . _:b419250879 . _:b419250878 . _:b419250243 . _:b419250873 . _:b419250647 . _:b419250872 . _:b419250875 . . _:b419250275 . _:b419250874 . _:b419250885 . _:b419250364 . . . _:b419250884 . _:b419250887 . . _:b419250886 . _:b419250881 . . _:b419250880 . _:b419250546 . _:b419250883 . . _:b419250882 . _:b419250893 . . . . _:b419250892 . _:b419250895 . _:b419250894 . _:b419251200 . _:b419250889 . . . _:b6461032 . _:b419250888 . _:b419250891 . _:b419250890 . _:b419250901 . . _:b419250639 . . _:b419250900 . _:b419250903 . _:b419250399 . _:b419250902 . _:b419250897 . _:b419250896 . _:b419250428 . . . _:b419250899 . . _:b419250066 . . _:b419250898 . _:b419250909 . _:b419250149 . _:b419250908 . _:b419250214 . . _:b419250911 . . _:b419250910 . _:b419250905 . _:b419251000 . _:b419250576 . _:b419250904 . _:b419250907 . _:b419250785 . _:b419250906 . . _:b419250917 . . _:b419250125 . . _:b419250827 . . _:b419250916 . _:b419250919 . _:b419250918 . _:b419250913 . . _:b419250912 . _:b419251156 . _:b419250915 . . _:b419250914 . _:b419250925 . _:b419250240 . _:b419250924 . _:b419251041 . _:b419250794 . _:b419250927 . . _:b419250926 . _:b419250921 . _:b419250920 . . _:b419250923 . . _:b419250922 . . _:b419250933 . _:b419250932 . _:b419250935 . _:b419250934 . _:b419250227 . _:b419250929 . . _:b419250928 . _:b419250931 . _:b419250865 . _:b419250930 . _:b419250104 . . _:b419250806 . _:b419250941 . _:b419250726 . _:b419250940 . _:b419250943 . . _:b419250444 . . _:b419250942 . . _:b419250937 . . _:b419250936 . _:b419250293 . _:b419250939 . _:b419250938 . . _:b419250437 . _:b419250817 . . _:b419251032 . _:b419250436 . _:b419250439 . . _:b419250438 . _:b419250522 . . _:b419250433 . _:b419250584 . _:b419250432 . . . _:b419250435 . _:b419250434 . _:b419250313 . _:b6461044 . _:b419250445 . . . _:b419250444 . . _:b419250447 . . . _:b419250446 . . _:b419250441 . _:b419251169 . _:b419250440 . _:b419250461 . _:b419250443 . _:b419250442 . _:b419250453 . _:b419250624 . _:b419250452 . _:b419251091 . _:b419250455 . _:b419250122 . _:b419250454 . _:b419250449 . _:b419250448 . . . _:b419250451 . _:b419250523 . _:b419250636 . _:b419250450 . _:b419250461 . _:b419250938 . . _:b419250611 . _:b419250460 . _:b419250246 . _:b419250463 . _:b419251009 . _:b419250462 . _:b419250457 . _:b419251176 . _:b419250456 . . _:b419250459 . _:b419250458 . . . _:b419250469 . _:b6461021 . _:b419250468 . _:b419250471 . _:b419250067 . _:b419250470 . _:b419250465 . _:b419250464 . . _:b419250467 . _:b419251195 . _:b6461047 . _:b419250743 . _:b419250466 . _:b419251128 . _:b419250477 . _:b419250090 . _:b6461021 "results" . _:b419250476 . . _:b6461050 "Resveratrol, which was discovered in a small-molecule screen to be a Sirt1 activator (>>1<<), has drawn a great deal of interest for its therapeutic potential in treating metabolic disorders such as type 2 diabetes." . _:b419250479 . _:b419250478 . _:b419251094 . _:b6461028 "Sirt1 overexpression (35\u201337), AMPK activation (21,>>22<<,38), and resveratrol treatment (5,7) all improve glucose tolerance and insulin sensitivity." . _:b419250473 . _:b419250472 . . . _:b419250475 . . _:b419250474 . _:b6461073 . . _:b419250485 . _:b419250484 . . _:b419250487 . . _:b419250486 . . _:b419250712 . _:b419250481 . _:b419250480 . _:b419250570 . _:b6461049 "One target for treating metabolic disorders is Sirt1 (8), an NAD+-dependent protein deacetylase (>>48<<). Resveratrol, which was discovered in a small-molecule screen to be a Sirt1 activator (1), has drawn a great deal of interest for its therapeutic potential in treating metabolic disorders such as type 2 diabetes. By increasing" . . _:b419250483 . _:b419250482 . _:b419250378 . . _:b419250493 . _:b419250161 . _:b419250492 . _:b419251101 . _:b419250495 . . _:b419250483 . . _:b419250494 . _:b419250859 . _:b419250489 . _:b419250893 . _:b419250488 . _:b419250491 . . _:b419250490 . _:b419250501 . . _:b419250500 . _:b419250503 . . _:b419250502 . _:b419250497 . _:b419250496 . _:b419250959 . _:b419250499 . _:b419250498 . . . _:b419250509 . . . _:b419250508 . _:b419250511 . _:b419250510 . _:b419250505 . _:b419250504 . . . _:b419250739 . . _:b419250507 . _:b419250506 . _:b419250517 . . _:b419250516 . _:b419250225 . _:b419250519 . _:b419250430 . _:b419250518 . . _:b419250513 . _:b419250173 . . . _:b419250512 . . _:b419250515 . _:b419250514 . _:b419250525 . _:b419250524 . _:b419251166 . _:b419250527 . _:b419251010 . _:b419250217 . . . _:b419250526 . . _:b419250521 . _:b419250520 . _:b419250590 . _:b419250523 . _:b6461079 "Sirt1\u2212/\u2212 mouse embryonic fibroblasts (mefs) (>>31<<) were maintained in DMEM supplemented with 10% fetal bovine serum." . _:b419250522 . _:b419250533 . _:b419250532 . . _:b419250232 . _:b419250535 . _:b419250242 . _:b419250534 . . _:b419250529 . _:b419250528 . _:b419250637 . _:b419250531 . _:b419250568 . _:b419250530 . . _:b419250541 . _:b419250540 . . _:b419250543 . _:b419250542 . _:b419250131 . _:b419250537 . . _:b419250536 . _:b419250539 . _:b419251087 . . . _:b419250538 . _:b419250549 . _:b419250898 . _:b419250548 . _:b419250551 . . _:b6461021 . _:b6461022 . . _:b419250550 . _:b419250411 . _:b6461023 . _:b419250545 . _:b419250544 . _:b419250547 . _:b419250546 . _:b419250954 . _:b419251011 . . . _:b419250557 . _:b6461028 . _:b419250556 . _:b419250747 . _:b6461029 . _:b419250559 . _:b6461030 . _:b419250558 . _:b6461031 . _:b419250553 . . _:b419250278 . _:b6461024 . _:b419250552 . _:b6461025 . _:b419250555 . _:b419250786 . _:b6461026 . . _:b419250554 . _:b419250756 . _:b6461027 . _:b419250565 . _:b6461036 . _:b419250564 . _:b419250075 . _:b6461037 . _:b419250567 . _:b419251216 . _:b6461038 . _:b419250566 . . _:b6461039 . _:b419250561 . _:b6461032 . _:b419250560 . . _:b419250384 . _:b6461033 . _:b419250563 . _:b6461034 . _:b419250562 . . _:b6461035 . _:b419250573 . . _:b6461044 . _:b419250248 . _:b419250572 . _:b6461045 . _:b419250575 . _:b419250925 . _:b6461046 . _:b419250574 . _:b419250569 . _:b6461047 . . _:b6461040 . . _:b419250568 . _:b419250216 . _:b419250736 . . _:b6461041 . _:b419250571 . _:b419250996 . _:b6461042 . _:b419250570 . . _:b6461043 . _:b419250581 . . _:b6461052 . _:b419250580 . . . _:b6461053 . . _:b419250583 . _:b6461054 . _:b419250130 . _:b419250582 . _:b419250716 . _:b6461055 . _:b419250577 . _:b6461048 . _:b419250576 . _:b6461049 . . _:b419250579 . _:b6461050 . _:b419250578 . . _:b419250693 "2"^^ . _:b6461051 . _:b419250589 . _:b419250692 "2"^^ . _:b6461060 . _:b419250588 . . _:b419250695 "2"^^ . _:b6461061 . _:b419250591 . _:b419250694 "2"^^ . _:b6461062 . _:b419251113 . _:b419250590 . _:b419250961 . _:b419250689 "2"^^ . _:b6461063 . _:b419250585 . _:b419250929 . _:b419250688 "2"^^ . _:b6461027 . _:b6461056 . _:b419250584 . _:b419250691 "2"^^ . . _:b6461057 . _:b419250587 . _:b419250690 "2"^^ . . _:b6461058 . _:b419250586 . _:b419250701 "2"^^ . _:b6461059 . _:b419250597 . . _:b419250700 "2"^^ . _:b6461068 . _:b419250596 . . _:b419250703 "2"^^ . _:b6461069 . _:b419250599 . . _:b419250702 "2"^^ . _:b6461070 . _:b419250598 . _:b419250697 "2"^^ . _:b6461071 . _:b419250593 . _:b419250696 "2"^^ . _:b6461064 . _:b419250592 . _:b419250699 "2"^^ . _:b419251095 . _:b6461065 . _:b419250595 . _:b419250698 "2"^^ . _:b6461066 . _:b419250594 . _:b419250709 "2"^^ . _:b6461067 . _:b419250605 . . _:b419250708 "2"^^ . . _:b419250108 . _:b6461076 . _:b419250604 . _:b419250711 "2"^^ . _:b6461077 . _:b419250607 . _:b419250710 "2"^^ . _:b6461078 . _:b419250606 . _:b419250705 "2"^^ . _:b6461079 . _:b419250601 . _:b419250704 "2"^^ . _:b419251012 . _:b6461072 . _:b419251189 . _:b419250600 . _:b419250707 "2"^^ . _:b419250426 . _:b419250603 . _:b6461073 . _:b419250706 "2"^^ . . _:b6461074 . _:b419250602 . _:b419250717 "2"^^ . _:b419250948 . _:b6461075 . . _:b419250613 . _:b419250716 "2"^^ . _:b419250860 . _:b419250842 . _:b419250612 . _:b419251177 . _:b419250719 "2"^^ . _:b419250615 . _:b419250718 "2"^^ . _:b419250614 . _:b419250713 "2"^^ . . _:b419250609 . _:b419250192 . _:b419250712 "2"^^ . _:b419250628 . . _:b6461080 . _:b419250608 . _:b419250715 "2"^^ . . _:b419250611 . _:b419250714 "2"^^ . . _:b419250610 . _:b419250725 "2"^^ . _:b419250621 . _:b419250724 "2"^^ . . _:b419250620 . _:b419250727 "2"^^ . _:b419250623 . _:b419250726 "2"^^ . _:b419251182 . _:b419250622 . _:b419250721 "2"^^ . _:b419250617 . _:b419250720 "2"^^ . _:b419250616 . _:b419250723 "2"^^ . . . _:b419250619 . _:b419250722 "2"^^ . _:b419251083 . _:b419250868 . _:b419250618 . _:b419250733 "2"^^ . _:b419250629 . _:b419250732 "2"^^ . _:b419250628 . _:b419250735 "2"^^ . . _:b419250631 . _:b6461025 "To determine whether the requirement of AMPK for the resveratrol effect is cell autonomous, we treated mefs developed from AMPK\u03B11/\u03B12 double knockout (>>32<<) and wild-type embryos with resveratrol for 6\u201324 h." . _:b419250734 "2"^^ . _:b419251104 . _:b419251210 . _:b419250126 . . _:b419250630 . . _:b419250729 "2"^^ . _:b419250625 . _:b419251133 . _:b419250728 "2"^^ . _:b6461071 "In skeletal muscle, the AMPK\u03B11 isoform makes up only \u223C20% of the total AMPK activity (>>17<<), and, yet, resveratrol-induced mitochondrial biogenesis (Fig." . _:b419250624 . _:b419250731 "2"^^ . _:b419250627 . _:b419250730 "2"^^ . _:b419250626 . _:b419250741 "2"^^ . . _:b419250637 . _:b419250740 "2"^^ . . . _:b419250636 . _:b419250743 "2"^^ . _:b419250639 . _:b419250742 "2"^^ . . _:b419250638 . _:b419250117 . _:b419250737 "2"^^ . . _:b419250633 . _:b419250736 "2"^^ . _:b419250632 . _:b419250696 . _:b419250739 "2"^^ . _:b419250635 . _:b419250738 "2"^^ . . _:b419250634 . _:b419250749 "2"^^ . . _:b419250645 . _:b419250748 "2"^^ . . _:b419250644 . . _:b419250751 "2"^^ . _:b419250647 . _:b419250750 "2"^^ . _:b419250646 . _:b419250745 "2"^^ . _:b419250641 . _:b419250744 "2"^^ . _:b419250534 . _:b419250640 . _:b419250747 "2"^^ . _:b419250643 . _:b419250746 "2"^^ . _:b419250642 . _:b419250757 "2"^^ . _:b419250653 . _:b419250756 "2"^^ . _:b419250652 . _:b419250759 "2"^^ . _:b419250655 . _:b419250758 "2"^^ . _:b419250654 . . _:b419250753 "2"^^ . _:b419250526 . _:b419250649 . . _:b419250752 "2"^^ . _:b419250648 . _:b419250755 "2"^^ . _:b419250651 . . _:b419250754 "2"^^ . _:b419250737 . _:b419250989 . . _:b419250650 . _:b419250765 "2"^^ . _:b419250661 . _:b419250764 "2"^^ . _:b419250660 . _:b419250767 "2"^^ . _:b419250663 . _:b419250766 "2"^^ . _:b6461030 "Sirt1 overexpression (35\u201337), AMPK activation (21,22,38), and resveratrol treatment (>>5<<,7) all improve glucose tolerance and insulin sensitivity." . _:b419250662 . _:b419250761 "2"^^ . _:b419250657 . _:b419250760 "2"^^ . _:b419250521 . _:b419250656 . _:b419250496 . _:b419250763 "2"^^ . _:b419250377 . _:b419250659 . _:b419250762 "2"^^ . _:b419250658 . _:b419250773 "2"^^ . _:b419250669 . _:b419250772 "2"^^ . _:b419250668 . _:b419250775 "2"^^ . . _:b419250671 . _:b419250774 "2"^^ . . . _:b419250109 . _:b419250670 . _:b419250769 "2"^^ . _:b419250665 . . _:b419250768 "2"^^ . . _:b419250664 . _:b419250771 "2"^^ . _:b419250667 . _:b419250770 "2"^^ . _:b419250666 . _:b419250781 "2"^^ . _:b419250677 . _:b419250780 "2"^^ . _:b419250676 . _:b419250783 "2"^^ . . _:b419250306 . _:b419250679 . _:b419250782 "2"^^ . _:b419250678 . _:b419250777 "2"^^ . . _:b419250673 . _:b419250776 "2"^^ . _:b419251031 . . _:b6461071 . _:b419250672 . _:b419250779 "2"^^ . _:b419250675 . _:b419250778 "2"^^ . _:b419250615 . _:b419250674 . _:b419250796 . _:b419250789 "2"^^ . . _:b419250832 . _:b419250685 . . _:b419250788 "2"^^ . _:b419250641 . _:b419250684 . _:b419250791 "2"^^ . . _:b419250687 . _:b419250790 "2"^^ . _:b419250686 . _:b6461080 "AMPK\u03B11/\u03B12 double knockout and wild-type mefs were derived as previously described (>>32<<). Cells were treated with 50 \u03BCmol/l resveratrol (Sigma) or DMSO for the indicated time. C2C12 myoblast cells (ATCC) were maintained in DMEM and 10% FBS. To generate C2C12 myotubes, a confluent culture of C2C12 cells were grown in DMEM and" . _:b419250785 "2"^^ . _:b419250681 . _:b419250784 "2"^^ . . _:b419250396 . _:b419250758 . _:b419250691 . _:b419250680 . _:b419250787 "2"^^ . _:b419250683 . _:b419250786 "2"^^ . _:b419250682 . _:b419250797 "2"^^ . _:b419250848 . _:b419250181 . _:b419250796 "2"^^ . _:b419250180 . _:b419251026 . _:b419250799 "2"^^ . _:b419250879 . _:b419251017 . _:b419250183 . _:b419250798 "2"^^ . _:b419250182 . _:b419250793 "2"^^ . . . _:b419250177 . _:b419250792 "2"^^ . _:b419250176 . _:b419250795 "2"^^ . _:b419250179 . _:b419250794 "2"^^ . _:b419250178 . _:b419250805 "2"^^ . _:b419250189 . _:b419250804 "2"^^ . _:b419250857 . . _:b419250188 . _:b419250807 "2"^^ . _:b419250552 . _:b419250284 . _:b419250191 . _:b419250806 "2"^^ . _:b419250773 . _:b419250190 . _:b419250801 "2"^^ . _:b6461072 . _:b419250185 . _:b419250800 "2"^^ . _:b419250717 . _:b419250184 . _:b419250803 "2"^^ . _:b419251079 . _:b419250187 . _:b419250802 "2"^^ . . _:b419250980 . _:b6461022 "As reported previously (>>7<<), resveratrol increased physical endurance (309.2 \u00B1 37 vs. 212.3 \u00B1 19 m) (Fig. 3A) of wild-type mice." . _:b419250186 . _:b419250813 "2"^^ . _:b419250339 . . _:b419250197 . _:b419250812 "2"^^ . . _:b419250196 . . _:b419250815 "2"^^ . _:b419250199 . _:b419250814 "2"^^ . . _:b419250198 . _:b419250809 "2"^^ . _:b419251214 . _:b419250193 . . . _:b419250808 "2"^^ . . . _:b419250192 . _:b419250811 "2"^^ . _:b419250195 . _:b419250810 "2"^^ . _:b419250912 . _:b419250766 . _:b419250194 . _:b419250821 "2"^^ . _:b419250071 . _:b419250205 . . _:b419250820 "2"^^ . _:b419250204 . _:b419250823 "2"^^ . _:b419250600 . _:b419250207 . . _:b419250822 "2"^^ . . _:b419250423 . _:b419250420 . _:b419250095 . . _:b419250206 . _:b419250817 "2"^^ . _:b419250201 . _:b419250816 "2"^^ . _:b419250200 . _:b419250819 "2"^^ . _:b419250969 . _:b419250203 . _:b419250818 "2"^^ . . _:b419250202 . _:b419250829 "2"^^ . _:b419250213 . _:b419250828 "2"^^ . _:b419250212 . _:b419250831 "2"^^ . _:b419250215 . _:b419250830 "2"^^ . _:b419250788 . . . _:b419250214 . _:b419250825 "2"^^ . _:b419250209 . _:b419250824 "2"^^ . . . _:b419250208 . _:b419250827 "2"^^ . . . _:b419250211 . _:b419250826 "2"^^ . . _:b419250210 . _:b419250837 "2"^^ . . _:b419250279 . _:b419250221 . _:b419250836 "2"^^ . . _:b419250220 . _:b419250839 "2"^^ . _:b419250223 . _:b419250838 "2"^^ . _:b419250222 . _:b419250833 "2"^^ . . _:b419250271 . _:b419250217 . _:b419250832 "2"^^ . _:b419250216 . _:b419250835 "2"^^ . _:b419250219 . _:b419250834 "2"^^ . . _:b419250850 . _:b419250218 . _:b419250845 "2"^^ . _:b419250229 . . _:b419250844 "2"^^ . . _:b419250459 . _:b419250228 . _:b419250847 "2"^^ . . _:b419250231 . _:b419250846 "2"^^ . _:b419250765 . _:b419250230 . _:b419250869 . _:b419250841 "2"^^ . _:b419250225 . _:b419250840 "2"^^ . _:b419250905 . _:b419250224 . _:b419250843 "2"^^ . _:b419250227 . _:b419250842 "2"^^ . . _:b419250226 . _:b419250853 "2"^^ . _:b6461059 "Therefore, the Sirt1 knockin model (>>36<<) cannot distinguish between a direct effect of Sirt1 and an indirect one caused by reduced fat." . . _:b419250237 . _:b419250795 . _:b419250852 "2"^^ . _:b419250236 . _:b419250855 "2"^^ . _:b419250239 . _:b419250854 "2"^^ . _:b419250238 . _:b419250849 "2"^^ . _:b419250342 . _:b419250233 . _:b419250848 "2"^^ . _:b419250232 . _:b419250851 "2"^^ . . _:b419250235 . _:b419250850 "2"^^ . _:b419250234 . _:b419250861 "2"^^ . . _:b419250245 . _:b419250860 "2"^^ . _:b419250244 . _:b419250863 "2"^^ . _:b419251065 . _:b6461043 . _:b419250247 . _:b419250862 "2"^^ . _:b419250246 . _:b419250363 . _:b419250857 "2"^^ . _:b419250512 . _:b419250241 . _:b419250856 "2"^^ . _:b419250723 . _:b419250240 . _:b419250859 "2"^^ . _:b419251118 . _:b419250243 . . _:b419250858 "2"^^ . _:b419250242 . _:b419250869 "2"^^ . _:b419250253 . _:b419250868 "2"^^ . _:b419250475 . _:b419250252 . _:b419250871 "2"^^ . _:b419250991 . _:b419250255 . _:b419250870 "2"^^ . _:b419250254 . _:b419250865 "2"^^ . . _:b419251168 . _:b419250249 . _:b419250864 "2"^^ . _:b419250248 . _:b419250867 "2"^^ . _:b419250251 . _:b419250866 "2"^^ . _:b6461062 . . _:b419250250 . _:b419250877 "2"^^ . _:b419250261 . _:b419250876 "2"^^ . _:b419250818 . _:b419250260 . _:b419250879 "2"^^ . . _:b419250263 . _:b419250878 "2"^^ . _:b419250680 . . _:b419250262 . _:b419250873 "2"^^ . _:b419250257 . _:b419250872 "2"^^ . _:b419250256 . _:b419250875 "2"^^ . _:b419250259 . _:b419250874 "2"^^ . _:b419250258 . _:b419250885 "2"^^ . _:b419250791 . _:b419250269 . _:b419250884 "2"^^ . _:b419250268 . _:b419250887 "2"^^ . _:b419250271 . _:b419250886 "2"^^ . _:b419250111 . _:b419250981 . _:b419250270 . _:b419250881 "2"^^ . _:b419250265 . _:b419250880 "2"^^ . _:b419250264 . _:b419250883 "2"^^ . _:b419250914 . _:b419250267 . _:b419250882 "2"^^ . . _:b419250266 . _:b419250893 "2"^^ . . _:b419250277 . _:b419250892 "2"^^ . _:b419250127 . _:b419250276 . _:b419250895 "2"^^ . . _:b419250279 . _:b419250894 "2"^^ . . _:b419250703 . _:b419251157 . _:b419250278 . _:b419250889 "2"^^ . . _:b419250273 . _:b419250888 "2"^^ . _:b419250272 . _:b419250891 "2"^^ . . _:b419250275 . _:b419250890 "2"^^ . . . _:b419250274 . _:b419250901 "2"^^ . _:b419250466 . . _:b419250285 . _:b419250900 "2"^^ . _:b419251207 . _:b419250284 . . _:b419250903 "2"^^ . _:b419251136 . . _:b419250287 . _:b419250902 "2"^^ . _:b419250107 . _:b6461055 "Surprisingly, the transgenic mice developed by Banks et al. (>>35<<), which are congenic in C57BL6/J background, have reduced metabolic rate and body temperature and have the same amount of fat despite eating less." . _:b419250286 . . _:b419250897 "2"^^ . _:b419250228 . _:b419250281 . _:b419250896 "2"^^ . _:b419250643 . _:b419250061 . _:b419250280 . _:b419250899 "2"^^ . _:b419250283 . _:b419250898 "2"^^ . _:b419250410 . _:b419250516 . _:b419250911 . _:b419250282 . _:b419250909 "2"^^ . _:b419250293 . _:b419250908 "2"^^ . _:b419250292 . _:b419250911 "2"^^ . . _:b419250295 . _:b419250910 "2"^^ . . _:b419250294 . _:b419250905 "2"^^ . _:b419250289 . _:b419250904 "2"^^ . _:b419250494 . _:b419250288 . _:b419250907 "2"^^ . . _:b419250810 . _:b419250291 . _:b419250906 "2"^^ . . _:b419250290 . _:b419250917 "2"^^ . _:b419250301 . _:b419250916 "2"^^ . _:b419250557 . _:b419250300 . _:b419250919 "2"^^ . _:b419250992 . _:b419250303 . _:b419250918 "2"^^ . _:b419250302 . _:b419250913 "2"^^ . _:b419251063 . _:b419250297 . _:b419250912 "2"^^ . _:b419250296 . _:b419250915 "2"^^ . _:b419250579 . _:b419250874 . _:b419250299 . _:b419250914 "2"^^ . . _:b419250539 . _:b419250298 . _:b419250925 "2"^^ . . _:b419250309 . _:b419250924 "2"^^ . . _:b419250308 . _:b419250927 "2"^^ . . . _:b419250311 . _:b419250926 "2"^^ . _:b419250062 . _:b419250310 . _:b419250921 "2"^^ . _:b419250701 . _:b419250787 . _:b419250305 . _:b419250920 "2"^^ . _:b419250304 . _:b419250923 "2"^^ . _:b419250219 . . _:b419250307 . _:b419250922 "2"^^ . _:b419250962 . _:b419250306 . _:b419250933 "2"^^ . . _:b419250317 . _:b419250932 "2"^^ . _:b419250316 . _:b6461079 . _:b419250935 "2"^^ . _:b419250297 . _:b419250319 . _:b419250934 "2"^^ . . _:b419250318 . _:b419250929 "2"^^ . . . _:b419250313 . . _:b419250928 "2"^^ . _:b419250360 . _:b419250312 . _:b419250931 "2"^^ . _:b419250315 . _:b419250930 "2"^^ . _:b419250314 . _:b419250941 "2"^^ . . _:b419250325 . _:b419250940 "2"^^ . _:b419250324 . _:b419250943 "2"^^ . . _:b419250327 . _:b419250942 "2"^^ . _:b419250326 . _:b419250937 "2"^^ . _:b419250321 . _:b419250936 "2"^^ . . . . _:b419250320 . _:b419250939 "2"^^ . . _:b419250323 . _:b419250938 "2"^^ . _:b419250322 . _:b419250949 "2"^^ . _:b419250569 . _:b419250333 . _:b419250948 "2"^^ . _:b419250480 . _:b419250332 . _:b419250951 "2"^^ . . _:b419250829 . _:b419250335 . . _:b419250950 "2"^^ . _:b419250157 . _:b419250334 . _:b419250945 "2"^^ . _:b419250329 . _:b419250944 "2"^^ . . _:b419250393 . _:b419250328 . _:b419250947 "2"^^ . _:b419250331 . _:b419250946 "2"^^ . _:b419250330 . _:b419250863 . _:b419250957 "2"^^ . . . _:b419250341 . _:b419250956 "2"^^ . _:b419250340 . _:b419250959 "2"^^ . _:b419250141 . . _:b419250343 . _:b419250958 "2"^^ . _:b419251096 . . _:b419250342 . _:b419250953 "2"^^ . _:b419251050 . . _:b419250337 . _:b6461026 . _:b419250952 "2"^^ . _:b419250336 . _:b419250955 "2"^^ . _:b419250404 . _:b419250339 . _:b6461052 . _:b419250954 "2"^^ . _:b419250338 . _:b6461055 . _:b419250965 "2"^^ . _:b419250349 . _:b419250964 "2"^^ . . _:b419250348 . _:b419250967 "2"^^ . _:b419250351 . _:b419250966 "2"^^ . _:b419250350 . _:b419250961 "2"^^ . _:b419250345 . _:b419250960 "2"^^ . _:b419251056 . . _:b419250344 . _:b419250963 "2"^^ . _:b419250347 . _:b419250807 . _:b419250962 "2"^^ . _:b419251209 . _:b419250346 . _:b419250926 . _:b419250973 "2"^^ . _:b419250357 . _:b419250972 "2"^^ . _:b419250575 . _:b419250356 . _:b6461067 "Resveratrol-induced physical endurance has been largely attributed to increased mitochondrial function (>>7<<). Certainly, converting muscle fiber to mitochondria-rich, slow-twitch fibers increases physical endurance (52)." . _:b419250975 "2"^^ . _:b419250118 . . . _:b419250359 . . _:b419250974 "2"^^ . _:b419250783 . _:b419250358 . _:b419250969 "2"^^ . . _:b419250353 . _:b419250195 . _:b419250968 "2"^^ . . . _:b419250352 . . _:b419250971 "2"^^ . . . . _:b419250355 . _:b419250970 "2"^^ . _:b419250354 . _:b419250981 "2"^^ . _:b419250365 . _:b419250980 "2"^^ . . _:b419250096 . _:b6461027 "Sirt1 overexpression (35\u201337), AMPK activation (>>21<<,22,38), and resveratrol treatment (5,7) all improve glucose tolerance and insulin sensitivity." . _:b419250364 . _:b419250997 . _:b419250983 "2"^^ . _:b419250776 . _:b419250367 . _:b419250982 "2"^^ . _:b419250366 . _:b419250977 "2"^^ . . _:b419251158 . _:b419250361 . _:b419250976 "2"^^ . _:b419250360 . _:b419250979 "2"^^ . . . _:b419250363 . _:b419250978 "2"^^ . _:b419250362 . _:b419250989 "2"^^ . _:b419251194 . _:b419250373 . _:b419250988 "2"^^ . _:b419250372 . _:b419250991 "2"^^ . _:b419250707 . . _:b419250375 . . _:b419250990 "2"^^ . _:b419250374 . _:b419250985 "2"^^ . _:b419251080 . _:b419250369 . _:b419250984 "2"^^ . _:b419250368 . _:b419250987 "2"^^ . _:b419250581 . _:b419250371 . _:b419250986 "2"^^ . _:b419250370 . _:b419250997 "2"^^ . . _:b419250381 . _:b419250996 "2"^^ . _:b6461056 "Nevertheless, this study shows that the function of Sirt1 on energy balance may be opposite of what was previously thought (>>7<<) and would be predicted if the central target of resveratrol was Sirt1." . _:b419250380 . _:b419250999 "2"^^ . _:b419250383 . _:b419250998 "2"^^ . _:b419250472 . _:b419250382 . _:b419250993 "2"^^ . _:b6461068 "Certainly, converting muscle fiber to mitochondria-rich, slow-twitch fibers increases physical endurance (>>52<<). However, it is also likely that the glycogen content in skeletal muscle, which is known to be increased by AMPK activity (34), also plays a role in resveratrol-induced physical endurance." . _:b419251131 . _:b419250168 . . _:b419250377 . _:b419250992 "2"^^ . _:b419250376 . _:b419250995 "2"^^ . _:b419250298 . _:b419250379 . _:b419250994 "2"^^ . _:b419250378 . _:b419251005 "2"^^ . . _:b419250389 . _:b419251004 "2"^^ . _:b419250388 . _:b419251007 "2"^^ . . . _:b419250391 . _:b419251006 "2"^^ . _:b419250725 . _:b419250390 . _:b419251001 "2"^^ . . _:b419250385 . _:b419251000 "2"^^ . . . _:b419250384 . _:b419251003 "2"^^ . _:b419250387 . _:b419251002 "2"^^ . . _:b419250565 . _:b419250386 . _:b419251013 "2"^^ . . _:b419250397 . _:b419251012 "2"^^ . . _:b419250396 . . _:b419251015 "2"^^ . . _:b419250399 . _:b419251014 "2"^^ . _:b419250398 . . _:b419251009 "2"^^ . _:b419250405 . _:b419250393 . _:b419251008 "2"^^ . _:b419250392 . _:b419251011 "2"^^ . . _:b419250395 . _:b419251010 "2"^^ . _:b419250394 . _:b419251021 "2"^^ . _:b419251072 . . _:b6461077 . _:b419250405 . _:b419251020 "2"^^ . . _:b419250404 . _:b419251023 "2"^^ . . _:b419250407 . _:b419251022 "2"^^ . _:b419250653 . _:b419250406 . _:b419251017 "2"^^ . . _:b419250401 . _:b419251016 "2"^^ . . . . _:b419250400 . _:b419251019 "2"^^ . _:b419250403 . _:b419251018 "2"^^ . _:b419250402 . _:b419251029 "2"^^ . _:b419250380 . _:b419250413 . . _:b419251028 "2"^^ . . . _:b419250412 . _:b419251031 "2"^^ . _:b419250415 . _:b419251030 "2"^^ . _:b419250414 . _:b419251025 "2"^^ . _:b419250409 . _:b419251024 "2"^^ . . _:b419250408 . _:b419251027 "2"^^ . _:b419250630 . . . _:b419250411 . _:b419251026 "2"^^ . _:b419250231 . _:b419250410 . _:b419251037 "2"^^ . _:b419250679 . _:b419250421 . _:b419251036 "2"^^ . . _:b419250614 . _:b419250420 . _:b419251039 "2"^^ . . _:b419250423 . _:b419251038 "2"^^ . . _:b419250422 . _:b419251033 "2"^^ . _:b419250417 . _:b419251032 "2"^^ . . _:b419250416 . _:b419251035 "2"^^ . _:b419250419 . _:b419251034 "2"^^ . _:b419250418 . _:b419251045 "2"^^ . _:b419250429 . _:b419251044 "2"^^ . _:b419250428 . _:b419251047 "2"^^ . _:b419250431 . _:b419251046 "2"^^ . _:b419250894 . _:b419250430 . _:b419251041 "2"^^ . . . _:b419250425 . _:b419251040 "2"^^ . . _:b419250947 . _:b419250626 . _:b419250424 . _:b419251043 "2"^^ . _:b419250427 . _:b419251042 "2"^^ . . _:b419250426 . _:b419251053 "2"^^ . _:b419251052 "2"^^ . _:b419251055 "2"^^ . . _:b419250465 . _:b419251054 "2"^^ . . _:b419251049 "2"^^ . . . _:b419251048 "2"^^ . _:b419251051 "2"^^ . _:b419251050 "2"^^ . _:b419250564 . _:b419250353 . _:b419251061 "2"^^ . _:b419251110 . . _:b419251060 "2"^^ . _:b419250388 . _:b419250389 . _:b419250390 . _:b419250391 . _:b419251063 "2"^^ . _:b419250384 . _:b419250385 . _:b419250386 . _:b419250387 . _:b419251062 "2"^^ . _:b419250396 . . _:b419250397 . _:b419250398 . _:b419250399 . _:b419251057 "2"^^ . _:b419250392 . _:b419250393 . _:b419250394 . _:b419250395 . _:b419251056 "2"^^ . _:b419250372 . _:b419250373 . _:b419250374 . _:b419250375 . _:b419250937 . _:b419251059 "2"^^ . _:b419250368 . _:b419250369 . _:b419250370 . _:b419250371 . . _:b419251058 "2"^^ . _:b419250380 . _:b419250381 . _:b419250382 . _:b419250383 . _:b419251069 "2"^^ . _:b419250376 . _:b419250148 . _:b419250377 . _:b419250378 . _:b419250085 . _:b419250379 . _:b419251068 "2"^^ . _:b419250420 . _:b419250421 . _:b419250422 . _:b419250423 . _:b419251071 "2"^^ . _:b419250416 . _:b419250417 . _:b419250418 . _:b419250419 . _:b419251070 "2"^^ . _:b419250428 . _:b419250429 . _:b419250430 . _:b419250431 . _:b419251065 "2"^^ . _:b419250424 . _:b419250425 . _:b419250426 . _:b419250427 . _:b419251064 "2"^^ . _:b419250404 . _:b419250405 . _:b419250406 . _:b419250407 . . _:b419251067 "2"^^ . _:b419250400 . _:b419250401 . _:b419250402 . _:b419250403 . _:b419251066 "2"^^ . _:b419250412 . _:b419250413 . _:b419250414 . _:b419250415 . _:b419251077 "2"^^ . _:b419250408 . _:b419250409 . _:b419250410 . . _:b419250411 . . _:b419251076 "2"^^ . _:b419250324 . _:b419250325 . _:b419250326 . _:b419250327 . _:b419251079 "2"^^ . . _:b419250320 . _:b419250321 . _:b419250322 . _:b419250323 . _:b419251078 "2"^^ . _:b419250332 . _:b419250333 . _:b419250334 . _:b419250335 . _:b419250798 . . _:b419251073 "2"^^ . _:b419250328 . _:b419250329 . _:b419250330 . _:b419250331 . _:b419251072 "2"^^ . _:b419250308 . _:b419250309 . _:b419250310 . _:b419250311 . _:b419251075 "2"^^ . _:b419250304 . _:b419250305 . _:b419250306 . . _:b419250307 . _:b419251074 "2"^^ . _:b419250316 . . _:b419250317 . _:b419250318 . _:b419250319 . _:b419251085 "2"^^ . _:b419250312 . _:b419250313 . _:b419250314 . _:b419250447 . _:b419250315 . . _:b419251084 "2"^^ . _:b419250356 . _:b419250357 . _:b419250358 . _:b419250359 . _:b419251087 "2"^^ . _:b419250352 . _:b419250353 . _:b419250354 . _:b419250355 . _:b419251086 "2"^^ . . . _:b419250364 . _:b419250365 . _:b419250366 . _:b419250367 . _:b419251081 "2"^^ . _:b419250360 . _:b419250361 . _:b419250105 . _:b419250362 . _:b419250363 . _:b419251080 "2"^^ . _:b419250340 . _:b419250341 . . _:b419250342 . _:b419250343 . _:b419251083 "2"^^ . _:b419250336 . _:b419250337 . _:b419250338 . _:b419250339 . _:b419251082 "2"^^ . _:b419250348 . _:b419250608 . _:b419250349 . _:b419250350 . _:b419250351 . _:b419251093 "2"^^ . _:b419250344 . . _:b419250345 . _:b419250346 . _:b419250562 . _:b419250347 . _:b419251092 "2"^^ . _:b419251023 . _:b419250260 . _:b419250261 . _:b419250262 . _:b419250263 . _:b419251095 "2"^^ . _:b419250256 . _:b419250729 . _:b419250257 . _:b419250258 . _:b419250259 . _:b419250663 . _:b419251094 "2"^^ . _:b419250268 . _:b419250269 . _:b419250270 . _:b419250271 . _:b419251089 "2"^^ . _:b419250264 . _:b419250265 . . . _:b419250266 . _:b419250267 . _:b419251088 "2"^^ . _:b419250588 . _:b419250244 . _:b419250119 . _:b419250245 . _:b419250246 . _:b419250541 . _:b419251091 "2"^^ . _:b419250247 . _:b419250240 . _:b419250241 . _:b419250242 . _:b419250243 . _:b419251090 "2"^^ . _:b419250252 . _:b419250253 . _:b419250254 . _:b419250255 . _:b419251101 "2"^^ . . . _:b419250248 . _:b419250249 . _:b419250250 . _:b419250251 . _:b419251100 "2"^^ . _:b419250292 . _:b419250293 . _:b419250294 . _:b419250295 . _:b419251037 . _:b419251103 "2"^^ . _:b419250288 . _:b419250289 . _:b419250290 . _:b419250291 . _:b419251102 "2"^^ . _:b419250300 . _:b419250301 . _:b419250302 . . _:b419250303 . . _:b419251097 "2"^^ . _:b419250296 . . _:b419250297 . _:b419250298 . _:b419250299 . _:b419251096 "2"^^ . _:b419250276 . _:b419250738 . _:b419250277 . _:b419250278 . . _:b419250279 . _:b419251099 "2"^^ . . _:b419250272 . _:b419250273 . _:b419250274 . _:b419250275 . _:b419251098 "2"^^ . _:b419250284 . _:b419250224 . . _:b419250307 . _:b419250285 . _:b419250286 . _:b419250287 . _:b419251109 "2"^^ . _:b419250280 . _:b419250281 . _:b419250282 . _:b419250283 . _:b419251108 "2"^^ . _:b419250196 . _:b419250197 . _:b419250322 . _:b419250198 . _:b419250199 . _:b419251111 "2"^^ . _:b419250192 . _:b419250193 . _:b419250194 . _:b419250195 . _:b419251110 "2"^^ . _:b419250204 . _:b419250205 . _:b419250206 . _:b419250207 . . _:b419251105 "2"^^ . _:b419250200 . . _:b419250201 . _:b419250202 . . _:b419250203 . _:b419251104 "2"^^ . _:b419250180 . _:b419250181 . _:b419250182 . _:b419250183 . _:b419251107 "2"^^ . _:b419250176 . _:b419250177 . _:b419250178 . _:b419250179 . _:b419251106 "2"^^ . _:b419250188 . _:b419250189 . . _:b419250190 . _:b419251171 . _:b419250191 . _:b419251117 "2"^^ . _:b419250184 . _:b419250185 . _:b419250186 . _:b419250187 . _:b419251116 "2"^^ . . _:b419250228 . _:b419250229 . _:b419250230 . _:b419250231 . _:b419251119 "2"^^ . _:b419250224 . _:b419250582 . _:b419250225 . _:b419250226 . _:b419250227 . _:b419251118 "2"^^ . _:b419250236 . _:b419250237 . _:b419250238 . _:b419250239 . _:b419251113 "2"^^ . _:b419250232 . _:b419250233 . _:b419250234 . _:b419250235 . _:b419251112 "2"^^ . . _:b419250212 . _:b419250213 . _:b419250790 . _:b419250214 . _:b419250215 . _:b419251115 "2"^^ . _:b419250208 . _:b419250209 . _:b419250210 . _:b419250211 . _:b419251114 "2"^^ . _:b419250928 . _:b419250220 . _:b419250221 . . _:b419250222 . _:b419250223 . _:b419251125 "2"^^ . _:b419250216 . _:b419250217 . _:b419250218 . _:b419250219 . _:b419250642 . _:b419251124 "2"^^ . _:b419250644 . _:b419250206 . _:b419250645 . _:b419250646 . _:b419250647 . _:b419251043 . _:b419250401 . _:b419251127 "2"^^ . _:b419250640 . _:b419250641 . _:b419250642 . _:b419250643 . _:b419251126 "2"^^ . _:b419250652 . _:b419251165 . _:b419250653 . _:b419250654 . _:b419250655 . _:b419250652 . . _:b419251121 "2"^^ . _:b419250648 . _:b419250649 . _:b419250650 . _:b419250651 . _:b419250858 . _:b419251120 "2"^^ . _:b419250628 . _:b419250629 . _:b419250630 . _:b419250631 . _:b419251123 "2"^^ . _:b419250624 . . _:b419250625 . _:b419250599 . _:b419250626 . _:b419250627 . _:b419251122 "2"^^ . _:b419250636 . . . _:b419250637 . _:b419250638 . _:b419250639 . _:b419251133 "2"^^ . _:b419250632 . _:b419250633 . _:b419250634 . _:b419251217 . _:b419250635 . _:b419251132 "2"^^ . _:b419250676 . _:b419250677 . _:b419250267 . _:b419250678 . _:b419250679 . _:b419251135 "2"^^ . _:b419250672 . _:b419250673 . _:b419250674 . _:b419250675 . _:b6461066 . _:b419251134 "2"^^ . _:b419250684 . _:b419250685 . _:b419250686 . _:b419250687 . . _:b419251129 "2"^^ . _:b419250680 . . _:b419250681 . _:b419250682 . _:b419250504 . _:b419250683 . _:b419251128 "2"^^ . _:b419250660 . _:b419250677 . _:b419250661 . _:b419250662 . _:b6461042 "A previous report (>>7<<) has shown that resveratrol treatment leads to deacetylation of PGC-1\u03B1, suggesting that the catalytic activity of Sirt1 is increased by resveratrol." . _:b419251131 "2"^^ . _:b419250663 . _:b419250656 . _:b419250657 . _:b419250658 . _:b419250659 . _:b419251130 "2"^^ . _:b419250668 . _:b419250669 . _:b419250670 . _:b419250544 . _:b419250671 . . _:b419251141 "2"^^ . _:b419250664 . _:b419250665 . _:b419251132 . _:b419250666 . . _:b419250667 . _:b419251140 "2"^^ . _:b419250580 . _:b419250581 . _:b419250918 . _:b419250446 . _:b419250582 . _:b419250583 . _:b419251143 "2"^^ . _:b419250576 . _:b419250577 . _:b419250578 . _:b419250579 . _:b419251142 "2"^^ . _:b419250588 . _:b419250589 . _:b419250590 . . _:b419250591 . _:b419251137 "2"^^ . _:b419250584 . . _:b419250585 . _:b6461078 . _:b419250586 . _:b419250906 . _:b419250587 . _:b419251136 "2"^^ . _:b419250564 . . _:b419250565 . _:b419250566 . . _:b419250838 . _:b419250567 . _:b419251139 "2"^^ . _:b419250560 . _:b419250561 . _:b419250562 . _:b419250563 . _:b419251138 "2"^^ . _:b419250572 . _:b419250573 . _:b419250574 . _:b419250575 . _:b419251149 "2"^^ . _:b419250568 . . _:b419250569 . _:b419250570 . . _:b419251148 "2"^^ . _:b419250571 . _:b419250612 . _:b419250613 . _:b419250614 . . _:b419250615 . _:b419251151 "2"^^ . _:b419250283 . _:b419250608 . _:b419250609 . _:b419250610 . _:b419250611 . _:b419251150 "2"^^ . _:b419250620 . _:b419250621 . _:b419250622 . _:b419250623 . _:b419251145 "2"^^ . _:b419250616 . _:b419250617 . _:b419250618 . _:b419250784 . _:b419250619 . _:b419251144 "2"^^ . _:b419250596 . _:b419250330 . _:b419250597 . _:b419250598 . _:b419250599 . _:b419251147 "2"^^ . _:b419250592 . _:b419250593 . _:b419250594 . _:b419250595 . _:b419251146 "2"^^ . _:b419250604 . _:b419250605 . _:b419250606 . _:b419250607 . _:b419251157 "2"^^ . _:b419250600 . _:b419250601 . _:b419250602 . _:b419250603 . _:b419251156 "2"^^ . . _:b419250516 . _:b419250517 . _:b419250518 . _:b419250519 . . _:b419251159 "2"^^ . _:b419250512 . _:b419250513 . _:b419250514 . _:b419250146 . _:b419250515 . _:b419251158 "2"^^ . _:b419250735 . _:b419250524 . . _:b419250525 . _:b419250526 . _:b419250527 . _:b419251153 "2"^^ . _:b419250520 . _:b419250964 . _:b419250521 . _:b419250522 . _:b419250523 . _:b419251152 "2"^^ . _:b419250500 . _:b419250287 . _:b419250501 . _:b419250502 . _:b419250503 . . _:b419251155 "2"^^ . _:b419250496 . _:b419250497 . _:b419250498 . _:b419250499 . _:b419250152 . _:b419251154 "2"^^ . _:b419250508 . . _:b419250509 . _:b419250510 . _:b419250511 . _:b419251165 "2"^^ . _:b419250504 . _:b419250505 . _:b419250506 . _:b419250507 . _:b419251164 "2"^^ . _:b419250548 . _:b419250549 . _:b419250550 . _:b419250551 . _:b419251167 "2"^^ . _:b419250544 . _:b419250545 . . _:b419250546 . _:b419250106 . _:b419251166 "2"^^ . _:b419250547 . _:b419250556 . _:b419250557 . _:b419250558 . _:b419250559 . _:b419251161 "2"^^ . _:b419250552 . _:b419250553 . . _:b419250554 . _:b419250555 . _:b419251160 "2"^^ . _:b419250532 . _:b419250533 . _:b419250534 . _:b419250535 . _:b419251163 "2"^^ . . _:b419250528 . _:b419250529 . _:b419250530 . _:b419250286 . _:b419250531 . _:b419251162 "2"^^ . _:b419250540 . _:b419250541 . _:b419250542 . _:b419250543 . _:b419251173 "2"^^ . _:b419250536 . _:b419250537 . _:b419250538 . _:b419250571 . _:b419250539 . _:b419251172 "2"^^ . _:b419250452 . . _:b419250453 . _:b419250454 . . _:b419250455 . _:b419250833 . _:b419251175 "2"^^ . _:b419250448 . _:b419250449 . _:b419250450 . _:b419250698 . _:b419250451 . _:b419251174 "2"^^ . _:b419250460 . . _:b419250461 . _:b419250669 . _:b419250462 . _:b6461034 . _:b419251169 "2"^^ . _:b419250463 . _:b419250456 . _:b419250457 . _:b419250458 . _:b419250459 . _:b419251168 "2"^^ . _:b419250436 . _:b419250437 . _:b419250438 . . _:b419250439 . _:b419251055 . _:b419251171 "2"^^ . _:b419250099 . _:b419250474 . _:b419250432 . _:b419250433 . _:b419250434 . _:b6461053 "More recently, transgenic mice in which the Sirt1 transgene is expressed from its own promoter have been reported by two independent groups (35,>>37<<). These transgenic mice, which have a more physiological expression pattern of the Sirt1 transgene than the knockin mice (36), are more insulin sensitive partly due to increased adiponectin levels and decreased hepatic steatosis." . _:b419250435 . . _:b419251170 "2"^^ . _:b419250444 . _:b419250445 . _:b419250446 . _:b419250447 . _:b419251181 "2"^^ . _:b419250440 . _:b419250441 . . _:b419250442 . _:b419250443 . _:b419251180 "2"^^ . _:b419250254 . _:b419250484 . . _:b419250485 . _:b419250486 . _:b419250487 . _:b419251183 "2"^^ . _:b419250480 . _:b419250481 . _:b419250482 . _:b419250281 . _:b419251182 "2"^^ . _:b419250483 . _:b419250492 . _:b419250493 . _:b419250494 . _:b419250495 . _:b419251177 "2"^^ . _:b419250488 . _:b419250489 . _:b419250490 . _:b419250491 . _:b419251176 "2"^^ . _:b419250468 . _:b419250469 . _:b419250470 . _:b419250471 . _:b419251179 "2"^^ . _:b419250464 . _:b419250465 . _:b419250466 . _:b419250467 . _:b419250518 . _:b419251178 "2"^^ . _:b419250476 . . _:b419250477 . _:b419250478 . _:b419250479 . _:b419251189 "2"^^ . _:b419250472 . _:b419250473 . _:b419251081 . _:b419250474 . _:b419250475 . _:b419251188 "2"^^ . _:b419250900 . _:b419250901 . _:b419250902 . _:b419250903 . _:b419251191 "2"^^ . _:b419250896 . _:b419250897 . _:b419250898 . _:b419250899 . _:b419251190 "2"^^ . _:b419250908 . _:b419250087 . _:b419250909 . _:b419251097 . _:b419250889 . _:b419250910 . _:b419250911 . _:b419251185 "2"^^ . _:b419250904 . _:b419250375 . _:b419250920 . _:b419251116 . _:b419250905 . _:b419250906 . _:b419250907 . _:b419251184 "2"^^ . . . . _:b419250884 . _:b419250885 . _:b419250886 . _:b419250887 . _:b419251187 "2"^^ . _:b419250880 . _:b419250881 . _:b419250882 . . _:b419251186 "2"^^ . _:b419250883 . _:b419250892 . _:b419250893 . _:b419250894 . _:b419250895 . _:b419251197 "2"^^ . _:b419250888 . . _:b419250889 . _:b419250890 . _:b419251173 . _:b419250891 . _:b419251196 "2"^^ . _:b419250932 . _:b419250933 . _:b419250934 . _:b419250935 . _:b419251199 "2"^^ . _:b419250928 . _:b419250120 . _:b6461032 "C: Relative levels of ROS in skeletal muscle extracts from wild-type (WT) and AMPK\u03B11\u2212/\u2212 mice fed high-fat diet (\u25A1) alone or high-fat diet supplemented with resveratrol (\u25A0) as measured by DCF fluorescence (>>52<<) (n = 4\u20135 for each genotype)." . . _:b419250929 . _:b419250930 . _:b419250931 . _:b419251198 "2"^^ . _:b419250940 . _:b419250941 . _:b419250942 . _:b419250943 . _:b419251193 "2"^^ . _:b419250936 . _:b419250937 . _:b419250938 . _:b419250939 . _:b419251192 "2"^^ . _:b419250916 . _:b6461060 . _:b419250917 . _:b419250918 . _:b419250919 . _:b419251195 "2"^^ . _:b419250912 . _:b419250913 . _:b419250914 . _:b419250236 . _:b419250103 . _:b419251194 "2"^^ . _:b419250915 . _:b419250924 . . _:b419250300 . _:b419250925 . _:b419250926 . _:b419250927 . _:b419251109 . _:b419250920 . . _:b419250921 . _:b419250181 "4"^^ . _:b419250922 . _:b419250923 . _:b419250836 . _:b419250837 . _:b419250180 "4"^^ . _:b419250838 . _:b419250839 . _:b419250376 . _:b419250832 . _:b419250833 . _:b419250183 "4"^^ . _:b419250834 . _:b419250835 . . _:b419250844 . _:b419250845 . _:b419250182 "4"^^ . _:b419250846 . _:b419250847 . _:b419250840 . _:b419250841 . _:b419250177 "4"^^ . _:b419250842 . _:b419250843 . . . _:b419250820 . _:b419250821 . _:b419250176 "4"^^ . _:b419250822 . . _:b419250823 . _:b419250816 . _:b419250817 . _:b419250179 "4"^^ . _:b419250818 . _:b419250819 . _:b419250828 . _:b419250829 . _:b419250178 "4"^^ . _:b419250830 . _:b419250831 . _:b419250824 . _:b419250825 . _:b419250189 "4"^^ . _:b419250826 . . _:b419250827 . _:b419250868 . _:b419250869 . _:b419250188 "4"^^ . _:b419250870 . _:b419250871 . _:b419250864 . _:b419250865 . _:b419250191 "4"^^ . _:b419250866 . _:b419250867 . _:b419250876 . _:b419250649 . _:b419250190 "4"^^ . _:b419250877 . _:b419250878 . _:b419250879 . _:b419250872 . _:b419250873 . _:b419250185 "4"^^ . _:b419250874 . _:b419250875 . _:b419250852 . _:b419250402 . _:b419250184 "4"^^ . _:b419250853 . _:b419250854 . _:b419250506 . _:b419250855 . _:b419250848 . _:b419250849 . _:b419250187 "4"^^ . _:b419250850 . . _:b419250851 . _:b419250860 . _:b419250861 . . _:b419250186 "4"^^ . _:b419250862 . _:b419250863 . _:b419250238 . _:b419250856 . _:b419250857 . _:b419250197 "4"^^ . _:b419250858 . _:b419250859 . _:b419250063 . _:b419250772 . _:b6461064 "Moreover, AMPK can activate PGC-1\u03B1, one of Sirt1 substrates, by directly phosphorylating it (50,>>51<<), indicating that activation of AMPK can affect the Sirt1-dependent pathways in multiple ways." . _:b419250773 . . _:b419250196 "4"^^ . _:b419250774 . . _:b419250775 . _:b419250768 . _:b419250769 . _:b419250199 "4"^^ . _:b419250770 . _:b419250771 . _:b419250780 . _:b419250781 . _:b419250198 "4"^^ . _:b419250782 . _:b419250783 . _:b419250776 . _:b419250074 . _:b419250714 . _:b419250193 "4"^^ . _:b419250777 . _:b419250778 . _:b419251146 . _:b419250779 . _:b419250756 . _:b419250757 . _:b419250192 "4"^^ . _:b419250758 . . _:b419250759 . _:b419250752 . _:b419250753 . _:b419250517 . _:b419250195 "4"^^ . _:b419250754 . _:b419250755 . _:b419250764 . . _:b419250765 . _:b419250194 "4"^^ . _:b419250766 . _:b419250767 . _:b419250760 . _:b419250761 . _:b419250205 "4"^^ . _:b419250762 . _:b419250763 . _:b419250804 . _:b419250719 . _:b419250204 "4"^^ . _:b419250805 . _:b419250806 . _:b419250807 . _:b419250800 . _:b419250801 . _:b419250207 "4"^^ . _:b419250802 . _:b419251154 . _:b419250803 . . _:b419250812 . _:b419250813 . . . _:b419250206 "4"^^ . _:b419250814 . _:b419250815 . _:b419250808 . _:b419250809 . _:b419250201 "4"^^ . _:b419250810 . _:b419250811 . . _:b419250788 . _:b419250789 . _:b419250200 "4"^^ . _:b419250790 . _:b419250791 . _:b419250784 . _:b419250785 . _:b419250203 "4"^^ . _:b419250786 . _:b419250787 . _:b419250796 . _:b419250797 . _:b419250202 "4"^^ . _:b419250798 . _:b419250799 . _:b419250792 . _:b419250793 . _:b419250213 "4"^^ . _:b419250794 . _:b419250795 . _:b419250708 . _:b419250709 . _:b419250212 "4"^^ . _:b419250710 . _:b419250711 . _:b419250704 . _:b419250705 . _:b419250215 "4"^^ . _:b419250706 . _:b419251100 . _:b419250707 . _:b419250716 . _:b419250717 . _:b419250214 "4"^^ . . _:b419250718 . _:b419250719 . _:b419250712 . _:b419250713 . _:b419250209 "4"^^ . _:b419250714 . _:b419250715 . . _:b419250692 . _:b419250693 . _:b419250208 "4"^^ . _:b419250694 . _:b419250695 . _:b419250688 . _:b419250689 . _:b419250211 "4"^^ . _:b419250690 . _:b419250691 . _:b419250700 . _:b419250317 . _:b419250701 . _:b419250210 "4"^^ . _:b419250702 . _:b419250703 . . _:b419250696 . _:b419250697 . _:b419250221 "4"^^ . _:b419250503 . _:b419250698 . _:b419250699 . _:b419250740 . _:b419250741 . _:b419250536 . _:b419250220 "4"^^ . _:b419250742 . _:b419250743 . _:b419250736 . _:b419250737 . _:b419250223 "4"^^ . _:b419250738 . _:b419250739 . _:b419250748 . _:b419250749 . _:b419250222 "4"^^ . _:b419250750 . _:b419250751 . _:b419250744 . . _:b419250217 "4"^^ . _:b419250745 . _:b419250746 . _:b419250747 . _:b419250724 . _:b419250725 . _:b419250216 "4"^^ . _:b419250726 . _:b419250727 . _:b419250720 . _:b419250721 . _:b419250219 "4"^^ . _:b419250722 . _:b419250723 . _:b419250732 . _:b419250733 . _:b419250218 "4"^^ . _:b419250734 . _:b419250735 . _:b419250728 . _:b419250772 . _:b419250729 . _:b419250229 "4"^^ . _:b419250730 . _:b419250274 . _:b419250731 . _:b419251156 . _:b419251157 . _:b419250228 "4"^^ . _:b419251158 . _:b419251159 . _:b419251152 . _:b419251153 . _:b419250231 "4"^^ . _:b419250984 . _:b419251154 . _:b419251155 . _:b419251164 . _:b419251165 . _:b419250230 "4"^^ . _:b419251166 . _:b419251167 . _:b419251160 . _:b419251161 . _:b419250225 "4"^^ . _:b419251162 . _:b419251163 . _:b419251140 . _:b419251141 . _:b419250224 "4"^^ . _:b419251142 . _:b419251143 . _:b419251136 . _:b419250080 . _:b419251137 . _:b419250227 "4"^^ . _:b419250678 . _:b419251138 . _:b419251139 . _:b419251148 . _:b419251149 . _:b419251175 . _:b419250226 "4"^^ . _:b419251150 . . _:b419251153 . . _:b419251151 . _:b419250887 . _:b419251144 . _:b419250223 . _:b419250237 "4"^^ . _:b419251145 . _:b419251146 . . _:b419251147 . _:b419251188 . _:b419250618 . _:b419250236 "4"^^ . _:b419251189 . _:b419251190 . _:b419251191 . _:b419251184 . _:b419251185 . _:b419250239 "4"^^ . _:b419251186 . _:b419251187 . _:b419251196 . _:b419251197 . _:b419250238 "4"^^ . _:b419251198 . _:b419251199 . _:b419251192 . _:b419251193 . _:b419250233 "4"^^ . _:b419250686 . _:b419251194 . _:b419251195 . . _:b419251172 . _:b419250112 . _:b419250232 "4"^^ . _:b419251173 . _:b419251174 . _:b419251175 . . _:b419251168 . _:b419251169 . _:b419250235 "4"^^ . _:b419251170 . _:b419251171 . _:b419250528 . . _:b419251180 . _:b419251181 . _:b419250234 "4"^^ . _:b419251182 . _:b419251183 . _:b419251176 . . _:b419251177 . _:b419250245 "4"^^ . _:b419251178 . _:b419251179 . _:b419251092 . _:b419251093 . . . _:b419250244 "4"^^ . _:b419251094 . . _:b419251095 . _:b419251088 . . _:b419251089 . _:b419250247 "4"^^ . _:b419251090 . _:b419251091 . _:b419251100 . _:b419251101 . _:b419250246 "4"^^ . _:b419251102 . _:b419251103 . _:b419251096 . _:b419251097 . _:b419250241 "4"^^ . _:b419251098 . _:b419251099 . _:b419251076 . _:b419251077 . _:b419250836 . _:b6461033 . _:b419250240 "4"^^ . . _:b419251078 . _:b419251079 . _:b419250999 . . _:b419251072 . _:b419251073 . _:b419250243 "4"^^ . _:b419251074 . _:b419251075 . _:b419250856 . _:b419251084 . _:b419251085 . _:b419250242 "4"^^ . _:b419251086 . _:b419251087 . _:b419251080 . . _:b419250253 "4"^^ . _:b419251081 . _:b419251082 . _:b419251083 . _:b419251124 . . _:b419250252 "4"^^ . _:b419251125 . _:b419251126 . _:b419251127 . _:b419251120 . _:b419251121 . _:b419250255 "4"^^ . _:b419251122 . _:b419251123 . _:b419251132 . _:b419251133 . _:b419250254 "4"^^ . _:b419251134 . _:b419251135 . . _:b419251128 . _:b6461063 . _:b419251129 . _:b419250249 "4"^^ . _:b419251130 . _:b419251131 . . . _:b419251108 . _:b419251109 . _:b419250248 "4"^^ . _:b419251110 . _:b419251111 . _:b419251104 . _:b419251105 . _:b419250251 "4"^^ . _:b419251106 . _:b419251107 . _:b419251116 . _:b419251117 . _:b419250250 "4"^^ . _:b419251118 . _:b419251119 . _:b419251112 . _:b419250261 "3"^^ . _:b419251113 . _:b419251114 . _:b419251115 . _:b419251028 . _:b419250260 "3"^^ . _:b419251029 . _:b419251030 . _:b419251031 . _:b419251024 . _:b419250263 "3"^^ . _:b419250138 . _:b419251025 . _:b419251026 . _:b419251027 . _:b419251036 . _:b419250262 "3"^^ . _:b419251037 . _:b419251038 . _:b419251039 . _:b419251032 . _:b419251033 . _:b419250257 "4"^^ . _:b419251034 . . _:b419251035 . _:b419251012 . _:b419250429 . . _:b419251013 . . _:b419250256 "4"^^ . _:b419251014 . _:b419251015 . _:b419250979 . _:b419251008 . _:b419250259 "3"^^ . _:b419251009 . _:b419251010 . _:b419251011 . . _:b419250258 "3"^^ . _:b419251020 . _:b419251021 . . _:b419251022 . _:b419251023 . _:b419251016 . _:b419250269 "3"^^ . _:b419251017 . _:b419251018 . . _:b419251019 . _:b419251060 . _:b419250268 "3"^^ . _:b419251061 . _:b419251062 . . _:b419251063 . _:b419251056 . _:b419250271 "3"^^ . _:b419251057 . _:b419251058 . _:b419251059 . . _:b419251068 . _:b419250270 "3"^^ . _:b419251069 . _:b419251070 . _:b419251071 . _:b419251064 . _:b419250265 "3"^^ . _:b419251065 . _:b419251066 . _:b419251067 . . _:b419251044 . _:b419250264 "3"^^ . _:b419251045 . _:b419251046 . _:b419251047 . _:b419251040 . _:b419250267 "3"^^ . _:b419251041 . _:b419251042 . _:b419251043 . _:b419251052 . _:b419250266 "3"^^ . _:b419251053 . _:b419251054 . _:b419251055 . _:b419251048 . _:b419250277 "3"^^ . _:b419251049 . _:b419251050 . _:b419251051 . . _:b419250964 . _:b419250276 "3"^^ . _:b419250965 . _:b419250648 . _:b419250966 . . _:b419250967 . _:b419250189 . _:b419250279 "3"^^ . _:b419250960 . _:b419250961 . _:b419250962 . _:b419250963 . _:b419250972 . _:b419250278 "3"^^ . _:b419250973 . _:b419250974 . _:b419250975 . _:b419250968 . _:b419250273 "3"^^ . _:b419250969 . _:b419250970 . _:b419250971 . _:b419250948 . _:b419250272 "3"^^ . _:b419250949 . _:b419250950 . _:b419250951 . _:b419250944 . _:b419250275 "3"^^ . _:b419250945 . _:b419250946 . _:b419250947 . _:b419250956 . _:b419250274 "3"^^ . _:b419250957 . _:b419250958 . _:b419250959 . . _:b419250952 . . _:b419250285 "3"^^ . . _:b419250953 . _:b419250198 . _:b419250954 . _:b419250955 . _:b419250408 . _:b419250284 "3"^^ . _:b419250996 . _:b419250690 . _:b419250997 . _:b419250998 . _:b419250999 . _:b419250992 . _:b419250287 "3"^^ . . _:b419250993 . _:b419250994 . . _:b419250995 . _:b419250471 . _:b419251004 . _:b419250286 "3"^^ . _:b419251005 . _:b419251006 . . _:b419251007 . _:b419251000 . _:b419250281 "3"^^ . _:b419251001 . _:b419251002 . _:b419251003 . _:b419250176 . _:b419250980 . _:b419250280 "3"^^ . _:b419250981 . _:b419250982 . _:b419250983 . _:b419250976 . _:b419250283 "3"^^ . _:b419250977 . _:b419250978 . _:b419250979 . _:b419250988 . _:b419250282 "3"^^ . _:b419250989 . _:b419251188 . _:b419250990 . _:b419250991 . . _:b419250293 "3"^^ . _:b419250984 . _:b419250985 . _:b419251163 . _:b419250986 . _:b419250987 . _:b419250213 . _:b419250292 "3"^^ . _:b419250295 "3"^^ . _:b419250294 "3"^^ . _:b419250262 . . _:b419250289 "3"^^ . _:b419250288 "3"^^ . _:b419250670 . _:b419250291 "3"^^ . _:b419250290 "3"^^ . _:b419250301 "3"^^ . _:b419250300 "3"^^ . _:b419250303 "3"^^ . _:b419250302 "3"^^ . _:b419250297 "3"^^ . _:b419250296 "3"^^ . _:b419250299 "3"^^ . _:b419250298 "3"^^ . _:b419250871 . _:b419250309 "3"^^ . _:b419250760 . _:b419250308 "3"^^ . _:b419250311 "3"^^ . _:b419250068 . _:b419250310 "3"^^ . _:b419251112 . _:b419250305 "3"^^ . _:b419250304 "3"^^ . . _:b419250307 "3"^^ . _:b6461041 "Although this can be explained, at least in part, by the observation that resveratrol inhibits insulin secretion by inhibiting the electrical activity in the \u03B2-cells (>>44<<), more studies are required to fully understand the disparity between the insulin levels and insulin sensitivity in resveratrol-treated AMPK-null mice." . . _:b419250306 "3"^^ . _:b419250244 . _:b419250317 "3"^^ . _:b419250316 "3"^^ . _:b419250319 "3"^^ . _:b419250318 "3"^^ . _:b419250313 "3"^^ . _:b419250312 "3"^^ . . _:b419250814 . _:b419250315 "3"^^ . _:b419250314 "3"^^ . . _:b419250325 "3"^^ . . _:b419250324 "3"^^ . _:b419250134 . _:b419250327 "3"^^ . . . _:b419250326 "3"^^ . . _:b419250321 "3"^^ . _:b419250453 . _:b419250320 "3"^^ . _:b419250323 "3"^^ . _:b419250322 "3"^^ . _:b419250333 "3"^^ . _:b419251134 . . . _:b419250332 "3"^^ . . . _:b419250335 "3"^^ . _:b419250334 "3"^^ . _:b419250351 . _:b419251090 . _:b419250329 "3"^^ . . . _:b419250137 . _:b419250328 "3"^^ . _:b419250331 "3"^^ . _:b419250713 . _:b419250330 "3"^^ . _:b419250341 "3"^^ . _:b419250239 . . _:b419250340 "3"^^ . . _:b419251216 . _:b419250140 . _:b419250343 "3"^^ . _:b419251217 . _:b419250753 . _:b419250342 "3"^^ . _:b419250187 . . . _:b419250337 "3"^^ . . _:b419251204 . _:b419250336 "3"^^ . _:b419251205 . _:b419251206 . _:b419251207 . _:b419251200 . _:b419250339 "3"^^ . _:b419251201 . _:b419250826 . _:b419251202 . _:b419251203 . _:b419251212 . _:b419250338 "3"^^ . _:b419251213 . _:b419251214 . _:b419251215 . _:b419251208 . _:b419250349 "3"^^ . . _:b419251209 . _:b419251210 . _:b419251211 . _:b419250744 . _:b419250348 "3"^^ . _:b419250351 "3"^^ . . _:b419250350 "3"^^ . _:b419250345 "3"^^ . _:b419250344 "3"^^ . . _:b419250347 "3"^^ . _:b419250932 . _:b419250185 . . _:b419250346 "3"^^ . _:b419250091 . _:b419250357 "3"^^ . _:b419250356 "3"^^ . . . _:b419250359 "3"^^ . _:b419250358 "3"^^ . _:b419251183 . _:b419250268 . . _:b419250353 "3"^^ . _:b419251042 . . _:b419250343 . _:b419250352 "3"^^ . . _:b419250355 "3"^^ . _:b419250156 . _:b419250354 "3"^^ . _:b6461069 . . _:b419250365 "3"^^ . _:b419250364 "3"^^ . . _:b419250367 "3"^^ . _:b419250366 "3"^^ . . _:b419250361 "3"^^ . _:b419250360 "3"^^ . _:b419250363 "3"^^ . _:b419250537 . _:b419250362 "3"^^ . _:b419250373 "3"^^ . _:b419250372 "3"^^ . _:b419250375 "3"^^ . _:b419250374 "3"^^ . _:b419250443 . _:b419250369 "3"^^ . _:b419250897 . _:b419250368 "3"^^ . _:b419250371 "3"^^ . _:b419251085 . . _:b419250370 "3"^^ . . _:b419250381 "3"^^ . _:b419250255 . _:b419250380 "3"^^ . _:b419250383 "3"^^ . _:b419250619 . _:b419250382 "3"^^ . _:b419250754 . _:b419250362 . _:b419250377 "3"^^ . . _:b419250376 "3"^^ . . _:b419250379 "3"^^ . . _:b419250385 . _:b419250378 "3"^^ . _:b419250389 "3"^^ . _:b419250302 . _:b419250388 "3"^^ . . . _:b419250661 . _:b419250391 "3"^^ . _:b419251107 . _:b419250390 "3"^^ . _:b419250365 . _:b419250385 "3"^^ . _:b419250069 . _:b419250384 "3"^^ . . _:b419250387 "3"^^ . _:b419250171 . _:b419251123 . . _:b419250386 "3"^^ . _:b419250397 "3"^^ . . _:b419250396 "3"^^ . _:b6461073 "research design and methods" . _:b419250399 "3"^^ . _:b419250398 "3"^^ . _:b419250462 . . _:b419250393 "3"^^ . . _:b419250968 . _:b419250392 "3"^^ . _:b419250081 . . _:b419250395 "3"^^ . _:b419250394 "3"^^ . _:b419251018 . _:b419250405 "3"^^ . _:b419250361 . _:b419251184 . _:b419250404 "3"^^ . _:b419250407 "3"^^ . _:b419250406 "3"^^ . . . _:b419250401 "3"^^ . . _:b419251206 . _:b419250400 "3"^^ . _:b419250403 "3"^^ . _:b419251212 . _:b419250402 "3"^^ . _:b419250413 "3"^^ . _:b419250412 "3"^^ . . _:b419250876 . _:b419251170 . _:b419250415 "3"^^ . _:b419250919 . _:b419250414 "3"^^ . _:b419250309 . . _:b419250409 "3"^^ . . _:b419250408 "3"^^ . _:b419250197 . . _:b6461026 "Sirt1 overexpression (>>35<<\u201337), AMPK activation (21,22,38), and resveratrol treatment (5,7) all improve glucose tolerance and insulin sensitivity." . _:b419250392 . _:b419250418 . _:b419250411 "3"^^ . . _:b419250410 "3"^^ . _:b419251135 . _:b419250421 "3"^^ . _:b419250196 . _:b419250420 "3"^^ . _:b419250423 "3"^^ . _:b419250950 . _:b419250422 "3"^^ . _:b419250417 "3"^^ . _:b419250416 "3"^^ . . _:b419250266 . _:b419250419 "3"^^ . _:b419250418 "3"^^ . _:b419250429 "3"^^ . _:b419250428 "3"^^ . _:b419250431 "3"^^ . _:b419250994 . . . . _:b419250881 . _:b419250430 "3"^^ . _:b419250775 . _:b419250674 . _:b419250425 "3"^^ . _:b419250358 . _:b419250424 "3"^^ . _:b419250427 "3"^^ . _:b419250174 . _:b419250426 "3"^^ . . _:b419250437 "3"^^ . _:b419250209 . _:b6461061 . _:b419250436 "3"^^ . _:b419250730 . _:b419250439 "3"^^ . _:b419250699 . _:b419250438 "3"^^ . _:b419250801 . _:b419250433 "3"^^ . _:b419250972 . _:b419250329 . _:b419250432 "3"^^ . _:b419251025 . . _:b419250435 "3"^^ . . _:b419250434 "3"^^ . . _:b419250493 . _:b419250445 "3"^^ . _:b419250444 "3"^^ . _:b419250447 "2"^^ . _:b419250446 "2"^^ . _:b419250441 "3"^^ . . _:b419250440 "3"^^ . _:b419250974 . . _:b419250764 . _:b419250443 "3"^^ . _:b419250442 "3"^^ . _:b419250453 "2"^^ . _:b419250654 . _:b419250258 . _:b419250452 . _:b419250452 "2"^^ . . _:b419250455 "2"^^ . . _:b419250841 . _:b419250454 "2"^^ . _:b419250449 "2"^^ . _:b419250448 "2"^^ . _:b419250451 "2"^^ . _:b419250450 "2"^^ . . . _:b419250461 "2"^^ . _:b419250460 "2"^^ . _:b419250463 "2"^^ . . . _:b419250462 "2"^^ . _:b419250930 . . _:b419251102 . _:b419250457 "2"^^ . . _:b419250460 . _:b419250456 "2"^^ . _:b419250311 . _:b419250459 "2"^^ . . _:b419250458 "2"^^ . _:b6461036 . _:b419250301 . _:b419250469 "2"^^ . . _:b6461035 . _:b419250468 "2"^^ . . _:b419250862 . _:b419250471 "2"^^ . . _:b419250470 "2"^^ . _:b419250340 . . _:b419250465 "2"^^ . _:b419250464 "2"^^ . _:b419250545 . _:b419250467 "2"^^ . . _:b419251142 . . _:b419250466 "2"^^ . _:b419250477 "2"^^ . . _:b419250212 . _:b419250476 "2"^^ . _:b419250479 "2"^^ . _:b419250431 . _:b419250290 . _:b419250515 . . _:b419250478 "2"^^ . _:b6461031 "Sirt1 overexpression (35\u201337), AMPK activation (21,22,38), and resveratrol treatment (5,>>7<<) all improve glucose tolerance and insulin sensitivity." . _:b419250473 "2"^^ . _:b419250718 . _:b419250472 "2"^^ . _:b419250475 "2"^^ . _:b419250474 "2"^^ . _:b419250485 "2"^^ . . _:b419250484 "2"^^ . _:b419251039 . _:b419250491 . _:b419250487 "2"^^ . _:b419250486 "2"^^ . _:b419250481 "2"^^ . _:b419250480 "2"^^ . _:b419250589 . _:b419250483 "2"^^ . . _:b419250482 "2"^^ . . . _:b419250493 "2"^^ . _:b419250403 . _:b419250492 "2"^^ . _:b419250374 . _:b419250495 "2"^^ . _:b419250494 "2"^^ . _:b419250489 "2"^^ . _:b419250488 "2"^^ . _:b419250491 "2"^^ . . _:b419250490 "2"^^ . _:b419250252 . _:b419250563 . _:b419250501 "2"^^ . . _:b419250500 "2"^^ . _:b419250503 "2"^^ . _:b419250907 . _:b419250502 "2"^^ . _:b419250497 "2"^^ . . _:b419250496 "2"^^ . . _:b419250831 . . _:b419250499 "2"^^ . . _:b419250498 "2"^^ . _:b419250822 . _:b419250509 "2"^^ . . _:b419250508 "2"^^ . _:b419250511 "2"^^ . _:b419250705 . _:b419250510 "2"^^ . _:b419250505 "2"^^ . _:b419251047 . _:b419250504 "2"^^ . _:b6461024 . . _:b419250507 "2"^^ . _:b419250506 "2"^^ . . _:b419251067 . _:b419250517 "2"^^ . _:b419250200 . _:b419250516 "2"^^ . _:b419250953 . _:b419250519 "2"^^ . _:b419250518 "2"^^ . _:b419250513 "2"^^ . _:b419250542 . _:b419250512 "2"^^ . . _:b419250515 "2"^^ . _:b419250514 "2"^^ . . _:b419250525 "2"^^ . _:b419250740 . _:b419250524 "2"^^ . _:b419251061 . _:b419250527 "2"^^ . . _:b419250277 . _:b419250526 "2"^^ . _:b419250308 . _:b419250521 "2"^^ . _:b419250520 "2"^^ . . _:b419250523 "2"^^ . . _:b419250522 "2"^^ . _:b419250533 "2"^^ . . _:b419251035 . . _:b419250532 "2"^^ . . _:b419250535 "2"^^ . . . _:b419250888 . _:b419250855 . _:b419250534 "2"^^ . _:b419250951 . _:b419250982 . . _:b419250529 "2"^^ . . _:b419250528 "2"^^ . . _:b419250531 "2"^^ . . _:b419250970 . _:b419250530 "2"^^ . _:b419250541 "2"^^ . _:b419250540 "2"^^ . _:b419251208 . _:b419250482 . _:b419250543 "2"^^ . . _:b419250542 "2"^^ . _:b419250354 . _:b419250537 "2"^^ . _:b419250536 "2"^^ . _:b419250539 "2"^^ . . _:b419250538 "2"^^ . . _:b419250549 "2"^^ . _:b419250548 "2"^^ . _:b419250551 "2"^^ . _:b419250899 . _:b419250550 "2"^^ . _:b419250545 "2"^^ . _:b419250623 . _:b419250544 "2"^^ . . _:b419250547 "2"^^ . . _:b419250546 "2"^^ . _:b419250557 "2"^^ . _:b419250823 . _:b419250556 "2"^^ . _:b419250559 "2"^^ . . _:b419250558 "2"^^ . _:b419250900 . _:b419250553 "2"^^ . _:b419250265 . _:b419250552 "2"^^ . _:b6461063 "Moreover, AMPK can activate PGC-1\u03B1, one of Sirt1 substrates, by directly phosphorylating it (>>50<<,51), indicating that activation of AMPK can affect the Sirt1-dependent pathways in multiple ways." . _:b419250160 . _:b419250555 "2"^^ . _:b419250554 "2"^^ . _:b419250488 . . _:b419250565 "2"^^ . _:b419250564 "2"^^ . _:b6461074 . _:b419250567 "2"^^ . _:b419250864 . _:b419250501 . _:b419250566 "2"^^ . . _:b419250561 "2"^^ . _:b419250179 . _:b419250560 "2"^^ . _:b419250226 . _:b419250563 "2"^^ . . _:b419250562 "2"^^ . . _:b419250573 "2"^^ . _:b419250572 "2"^^ . _:b419250327 . . _:b419250575 "2"^^ . . _:b419250574 "2"^^ . _:b419250406 . _:b419250569 "2"^^ . . _:b419250568 "2"^^ . _:b419250571 "2"^^ . _:b419250570 "2"^^ . _:b419251028 . _:b419250581 "2"^^ . . _:b6461024 "It is believed that the resveratrol effects are mediated by increased expression and function of PGC-1\u03B1, the master regulator of mitochondrial biogenesis and oxidative phosphorylation (>>34<<). We measured the expression of PGC-1\u03B1 and other resveratrol-induced genes critical for mitochondrial function in the skeletal muscle of resveratrol-treated AMPK-deficient mice. As shown in Fig. 3C, resveratrol induced the expression of" . _:b419250580 "2"^^ . . _:b419250583 "2"^^ . _:b419250100 . _:b419250582 "2"^^ . . _:b419250577 "2"^^ . _:b419250576 "2"^^ . _:b419250797 . _:b419250579 "2"^^ . _:b419250336 . . _:b419250456 . _:b419250578 "2"^^ . _:b419250668 . _:b419250589 "2"^^ . . _:b419250588 "2"^^ . . . _:b419250591 "2"^^ . _:b419250805 . . _:b419250590 "2"^^ . . _:b419250585 "2"^^ . . _:b419250584 "2"^^ . . _:b419250587 "2"^^ . . _:b419250566 . _:b419250276 . _:b419250586 "2"^^ . _:b419250151 . _:b419250940 . _:b419250597 "2"^^ . _:b419250596 "2"^^ . _:b419251084 . _:b419250599 "2"^^ . . _:b419250598 "2"^^ . _:b419250419 . _:b419250593 "2"^^ . _:b6461057 "One possible explanation for the reduced fat mass in the knockin mice (>>36<<) is that expression of the Sirt1 transgene from the \u03B2-actin locus impaired adipocyte differentiation during development (49)." . _:b419250592 "2"^^ . _:b419250595 "2"^^ . _:b419250594 "2"^^ . _:b419251199 . _:b419250605 "2"^^ . . _:b419250604 "2"^^ . . _:b419250607 "2"^^ . _:b419250606 "2"^^ . . _:b419250133 . _:b419250601 "2"^^ . _:b419250600 "2"^^ . . _:b419250603 "2"^^ . _:b419250178 . _:b6461047 _:b6461048 . _:b6461047 _:b6461049 . _:b6461047 _:b6461050 . _:b419250602 "2"^^ . _:b6461047 _:b6461051 . _:b6461047 _:b6461052 . _:b6461047 _:b6461053 . _:b6461047 _:b6461054 . _:b419250613 "2"^^ . . _:b6461047 _:b6461055 . _:b6461060 "Resveratrol has been reported to affect the activities of many enzymes (>>11<<) including AMPK (12). To evaluate the possibility that the effects of resveratrol are mediated by AMPK, we studied the effects of resveratrol in mice deficient in AMPK\u03B11 or -\u03B12." . _:b419250612 "2"^^ . _:b419250615 "2"^^ . _:b419250923 . _:b419250614 "2"^^ . . . _:b419250609 "2"^^ . _:b419250550 . _:b419250608 "2"^^ . _:b419250499 . . _:b419250611 "2"^^ . _:b419250610 "2"^^ . . _:b419250687 . _:b419250621 "2"^^ . _:b419251150 . _:b419250620 "2"^^ . _:b419250591 . _:b419250623 "2"^^ . _:b419251062 . _:b419250334 . _:b419250622 "2"^^ . . . _:b419250617 "2"^^ . _:b419250616 "2"^^ . _:b419250083 . _:b419250619 "2"^^ . . _:b419250618 "2"^^ . _:b419250629 "2"^^ . _:b419250388 . _:b419250628 "2"^^ . _:b419250861 . . _:b419250631 "2"^^ . _:b419250630 "2"^^ . . _:b419250625 "2"^^ . _:b419251044 . . _:b419250624 "2"^^ . _:b419250627 "2"^^ . . _:b419250551 . _:b419250626 "2"^^ . . _:b419250637 "2"^^ . _:b6461047 _:b6461072 . _:b419250636 "2"^^ . . _:b419250639 "2"^^ . _:b6461047 _:b6461064 . _:b6461047 _:b6461065 . _:b6461047 _:b6461066 . _:b419250638 "2"^^ . _:b6461047 _:b6461067 . _:b6461047 _:b6461068 . _:b419250922 . _:b6461047 _:b6461069 . _:b6461047 _:b6461070 . _:b419250633 "2"^^ . _:b6461047 _:b6461071 . . _:b6461047 _:b6461056 . _:b6461047 _:b6461057 . _:b6461047 _:b6461058 . _:b419250632 "2"^^ . _:b6461047 _:b6461059 . _:b6461047 _:b6461060 . _:b6461047 _:b6461061 . _:b6461047 _:b6461062 . _:b419250635 "2"^^ . _:b6461047 _:b6461063 . . _:b419250634 "2"^^ . _:b419250645 "2"^^ . . _:b419250644 "2"^^ . _:b419251049 . _:b6461021 _:b6461022 . _:b419250647 "2"^^ . _:b6461021 _:b6461023 . _:b419250646 "2"^^ . _:b419250530 . _:b419251078 . _:b419250641 "2"^^ . . _:b419250792 . _:b419250640 "2"^^ . _:b419251125 . _:b419250643 "2"^^ . . _:b419250326 . _:b6461021 _:b6461040 . . _:b6461021 _:b6461041 . _:b6461021 _:b6461042 . _:b419250642 "2"^^ . _:b6461021 _:b6461043 . _:b419250359 . _:b6461021 _:b6461044 . _:b419250763 . _:b6461021 _:b6461045 . _:b419251147 . _:b419250587 . _:b419250653 "2"^^ . _:b6461021 _:b6461046 . _:b419250819 . _:b419250652 "2"^^ . . _:b419250655 "2"^^ . _:b419250519 . _:b6461021 _:b6461024 . _:b6461021 _:b6461025 . _:b6461021 _:b6461026 . _:b419250654 "2"^^ . _:b6461021 _:b6461027 . _:b6461021 _:b6461028 . _:b6461021 _:b6461029 . _:b6461021 _:b6461030 . _:b419250649 "2"^^ . _:b6461021 _:b6461031 . . _:b6461021 _:b6461032 . _:b6461021 _:b6461033 . _:b6461021 _:b6461034 . _:b419250648 "2"^^ . . _:b6461021 _:b6461035 . _:b419250601 . _:b6461021 _:b6461036 . _:b6461021 _:b6461037 . _:b6461021 _:b6461038 . _:b6461070 . _:b419250651 "2"^^ . _:b6461021 _:b6461039 . . _:b419250650 "2"^^ . _:b419250661 "2"^^ . _:b419250660 "2"^^ . _:b419250663 "2"^^ . . . _:b419251007 . _:b419250662 "2"^^ . . _:b419250657 "2"^^ . . _:b419250166 . _:b419250656 "2"^^ . . _:b419250659 "2"^^ . _:b419250761 . _:b419250658 "2"^^ . _:b419250321 . _:b419250191 . . _:b419250669 "2"^^ . _:b419250668 "2"^^ . _:b419250895 . _:b6461058 . _:b419250671 "2"^^ . . . _:b6461073 _:b6461074 . . _:b419250670 "2"^^ . _:b6461073 _:b6461075 . _:b6461073 _:b6461076 . _:b6461073 _:b6461077 . _:b6461073 _:b6461078 . _:b419250665 "2"^^ . _:b6461073 _:b6461079 . . _:b6461073 _:b6461080 . _:b419250664 "2"^^ . _:b419250667 "2"^^ . _:b419250666 "2"^^ . _:b419250665 . . _:b419250172 . _:b419250677 "2"^^ . _:b419251172 . _:b419250676 "2"^^ . _:b419250679 "2"^^ . _:b419250678 "2"^^ . . _:b419250673 "2"^^ . _:b419250672 "2"^^ . _:b419250656 . _:b419250759 . _:b419250675 "2"^^ . _:b419250270 . _:b419250674 "2"^^ . _:b419250685 "2"^^ . . _:b419250684 "2"^^ . _:b419250687 "2"^^ . _:b419250285 . _:b419250686 "2"^^ . _:b419250681 "2"^^ . _:b419250741 . _:b419250680 "2"^^ . _:b419250683 "2"^^ . _:b419250682 "2"^^ . _:b419250872 . . . _:b419251159 . . . _:b6461047 "discussion" . . _:b419250407 . . . _:b419250580 . . . . _:b419250331 . _:b419250205 . . _:b6461030 . _:b419250513 . _:b419250870 . _:b419250985 . _:b419250527 . _:b419251074 . _:b419250484 . . . _:b419250944 . . . . . . _:b419250635 . . _:b6461028 . _:b419250442 . "PMC0" . . . . . . _:b419250821 . . . _:b419250597 . . . _:b419250645 . . _:b419250955 . _:b6461062 "The ability of AMPK to increase NAD and the NAD-to-NADH ratio (>>45<<) may also explain how resveratrol treatment can lead to Sirt1 activation without directly activating it." . . . . . . . _:b419250433 . _:b419250854 . _:b419250885 . . _:b419250958 . . _:b419250578 . _:b6461038 "Since resveratrol increases mitochondrial function (>>7<<), we measured the DAG and ceramide levels in resveratrol-treated skeletal muscle." . _:b419250884 . _:b6461040 "Adiponectin, a cytokine that is produced by fat and is decreased in obese and diabetic subjects (43), increases insulin sensitivity by activating AMPK (>>38<<). To determine whether resveratrol increased insulin sensitivity by increasing adiponectin levels, we measured serum adiponectin levels in resveratrol-treated mice. Adiponectin levels were similar for wild-type, AMPK\u03B11\u2212/\u2212, and AMPK\u03B12\u2212/\u2212" . _:b419251126 . . _:b419250489 . _:b419250449 . . . _:b419250634 . _:b419250371 . _:b419250390 . _:b419250732 . . . . _:b419250977 . _:b419250558 . _:b419250748 . _:b419250424 . _:b419251111 . . _:b419250427 . _:b419250458 . _:b419250921 . _:b419250965 . . _:b419250367 . _:b419250188 . . . . _:b6461054 "These transgenic mice, which have a more physiological expression pattern of the Sirt1 transgene than the knockin mice (>>36<<), are more insulin sensitive partly due to increased adiponectin levels and decreased hepatic steatosis." . _:b419250454 . _:b419250882 . . . _:b6461033 "Insulin-resistant states are associated with increased production of ROS, and reduction of ROS with antioxidants improves insulin sensitivity (>>39<<,40). Since resveratrol is thought to have antioxidant properties, it is possible that some insulin sensitizing of resveratrol effect may be related to its antioxidant effect." . _:b419250902 . _:b419250113 . _:b419251205 . . . _:b419250594 . . _:b419250839 . _:b419250700 . . _:b419250638 . . . . . . _:b6461050 . _:b419250303 . _:b419251174 . . . . . _:b419250851 . _:b419251152 . . _:b6461041 . _:b419250235 . _:b419250310 . . . . _:b419251108 . _:b419251140 . . _:b419251082 . _:b419251034 . . . _:b419251204 . . . _:b419250150 . . . _:b419251192 . . . _:b419250574 . . _:b419250064 . _:b419250249 . _:b419250779 . _:b419251076 . _:b419250834 . _:b419250199 . . _:b419250620 . _:b419250960 . . _:b419250437 . _:b419251155 . . . _:b419250468 . . _:b419250524 . . _:b419250136 .