title: Stilbene analogs of resveratrol improve insulin resistance through activation of AMPK.
abstract: Resveratrol (RSV), 3,5,4'-trihydroxy-trans-stilbene, is known to have many beneficial physiological activities. We have synthesized several stilbene analogues and have reported that the hydroxyl group in the 4' position of RSV exhibited strong radical scavenging action. Using stilbene analogs, we investigated the structure of RSV to explain its protective effect against obesity and type 2 diabetes. All six analogs used in this study inhibited the differentiation of 3T3-L1 adipocytes. 3-Hydroxy-trans stilbene (3(OH)ST), and 3,4'-dihydroxy-trans stilbene (3,4'(OH)2ST) increased glucose uptake and induced adenosine monophosphate kinase (AMPK) phosphorylation in C2C12 myotubes independently of insulin. An in vivo study using mice fed high-fat diets indicated that 3(OH)ST was more effective than RSV in improving insulin resistance. In conclusion, RSV and its derivatives, particularly 3(OH)ST, inhibited adipocyte differentiation and enhanced glucose uptake in the myotubes, resulting in a reduction of obesity and an improvement in glucose tolerance in vivo.
authors.affiliation: Department of Food and Nutritional Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ito-Nagahata
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kurihara
authors.forename: Miki
authors.initials: M
authors.lastname: Hasebe
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishii
authors.forename: Kaori
authors.initials: K
authors.lastname: Yamashita
authors.forename: Mari
authors.initials: M
authors.lastname: Iwabuchi
authors.forename: Mariko
authors.initials: M
authors.lastname: Sonoda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukuhara
authors.forename: Rumi
authors.initials: R
authors.lastname: Sawada
authors.forename: Atsuko
authors.initials: A
authors.lastname: Matsuoka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fujiwara
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D051379:Mice; D009765:Obesity / Q000188:drug therapy* / Q000473:pathology; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000138:chemical synthesis
chemical_list: D007328:Insulin; D013267:Stilbenes; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D000077185:Resveratrol