title: Effects of resveratrol in patients with type 2 diabetes mellitus on skeletal muscle SIRT1 expression and energy expenditure.
abstract: OBJECTIVE
  The primary aims of the study were to examine the effect of resveratrol on skeletal muscle SIRT1 expression and energy expenditure in subjects with Type 2 diabetes mellitus (T2DM).
  
  
  BACKGROUND
  Animal and in vivo studies indicate that resveratrol increases SIRT1 expression that stimulates PGC1α activity. Subsequent upregulation of AMPK and GLUT4 expression are associated with improved insulin sensitivity in peripheral tissues.
  
  
  METHODS
  Ten subjects with T2DM were randomized in a double-blind fashion to receive 3g resveratrol or placebo daily for 12 weeks. Secondary outcomes include measures of AMPK, p-AMPK and GLUT4 expression levels, energy expenditure, physical activity levels, distribution of abdominal adipose tissue and skeletal muscle fiber type composition, body weight, HbA1c, plasma lipid subfraction, adiponectin levels, and insulin sensitivity.
  
  
  RESULTS
  There was a significant increase in both SIRT1 expression (2.01 vs. 0.86 arbitrary units [AU], p = .016) and p-AMPK to AMPK expression ratio (2.04 vs. 0.79 AU, p = .032) in the resveratrol group compared with the placebo group. Although the percentage of absolute change (8.6 vs. -13.9%, p = .033) and percentage of predicted resting metabolic rate (RMR; 7.8 vs. -13.9%, p = .013) were increased following resveratrol, there was a significant reduction in average daily activity (-38 vs. 43.2%, p = .028) and step counts (-39.5 vs. 11.8%, p = .047) when compared with placebo.
  
  
  CONCLUSIONS
  In patients with T2DM, treatment with resveratrol regulates energy expenditure through increased skeletal muscle SIRT1 and AMPK expression. These findings indicate that resveratrol may have beneficial exercise-mimetic effects in patients with T2DM.
authors.affiliation: Division of Endocrinology, Khoo Teck Puat Hospital, Singapore.
authors.forename: Kian Peng
authors.initials: KP
authors.lastname: Goh
authors.forename: Hwei Yee
authors.initials: HY
authors.lastname: Lee
authors.forename: Dawn Pingxi
authors.initials: DP
authors.lastname: Lau
authors.forename: Wilma
authors.initials: W
authors.lastname: Supaat
authors.forename: Yiong Huak
authors.initials: YH
authors.lastname: Chan
authors.forename: Angela Fang Yung
authors.initials: AF
authors.lastname: Koh
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D001481:Basal Metabolism / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects*; D015444:Exercise; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D005082:Physical Exertion / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D012146:Rest; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D027843:Vitis / Q000737:chemistry
chemical_list: D051275:Glucose Transporter Type 4; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010936:Plant Extracts; C495692:SLC2A4 protein, human; D013267:Stilbenes; D014157:Transcription Factors; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol