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2010 Annual Meeting Abstracts

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Oral Resvaratrol Supplementation Reverses Glucose Intolerance: The Role of Skeletal Muscle and the Liver
*Michael P. Robich1, *Thomas A. Burgess2, *Louis M. Chu1, *Shizu Oyamada2, *Richard T. Clements2, Frank W. Sellke3
1Beth Israel Deaconess Medical Center, Boston, MA;2Rhode Island Hospital, Providence, RI;3Warren Alpert School of Medicine, Brown University, Providence, RI

Objective: Reversing the progression of glucose intolerance is thought to improve the risk of coronary artery disease. We hypothesized that supplemental resveratrol would affect glucose metabolism in the skeletal muscle and liver to improve blood glucose control.
Design: Animal study
Setting: Basic science laboratory
Interventions: Yorkshire swine were made pre-diabetic by excess calorie high-fat/cholesterol diet for 11 weeks. Pigs were fed either a normal diet (CTL, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCRV, n=7).
Main outcome measures: After 11 weeks, swine underwent intravenous glucose tolerance testing and skeletal muscle and liver were harvested to assess signaling related to glucose control.
Results: The HCC group had significantly increased blood glucose levels at 30 minutes as compared to the CTL and HCRV groups. The HCC group demonstrated increased serum levels of AST, ALT, and alkaline phosphatase. Oil red-O staining demonstrated increased lipid concentrations in the livers of the HCC animals. There were no histologic changes between groups on hematoxylin and eosin staining in the liver. Immunoblotting in the liver showed increased levels of mTOR, IRS-1, and phospho-Akt(Thr308) in the HRCV group. Immunoblotting in skeletal muscle tissue demonstrated increased Glut 4, PGC-1α, PPARα, PPARγ, and phospho-Akt(Thr308) levels as well as decreased RBP4 in the HCRV group. Immunofluorescence staining for Glut4 in the skeletal muscle demonstrated that HCC had large intracellular accumulations of Glut 4 while HCRV had a higher proportion of Glut 4 on the cell membrane than the HCC group.
Conclusion: Supplemental resveratrol influences glucose metabolism pathways in the liver and skeletal muscle and leads to improved glucose control in a swine model of glucose intolerance.

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