Roux-en-Y gastric bypass increases hepatic and peripheral insulin sensitivity in rats with type 2 diabetes mellitus

Background: Roux-en-Y gastric bypass (RYGB) surgery for the treatment of obesity leads to long-term diabetes remission in approximately 80% of cases. The aim of this study was to investigate the effects of RYGB on hepatic and peripheral insulin sensitivity in type 2 diabetic rats and their possible mechanisms. We also tested the hypothesis that RYGB reduces lipid content and improves insulin sensitivity in hepatocytes and skeletal muscle cells. Methods: Sprague-Dawley rats were divided into 4 groups: diabetic RYGB group (n = 18), diabetic RYGB sham group (n = 6), diabetic group (n = 6), and nondiabetic control group (n = 6). The hyperinsulinemic-euglycemic clamp with tracer infusion was completed at 2, 4, and 8 weeks postoperatively to assess insulin sensitivity. The lipid content in liver and muscle tissue was examined. Results: Postoperatively, the diabetic RYGB group had significant decreases in weight, fat mass, and food intake. Two weeks after surgery, RYGB had significantly improved the hepatic insulin sensitivity index and decreased the hepatic tiglyceride, total cholesterol, and fatty acyl-CoA content. The significantly increased insulin sensitivity and decreased lipid content in muscle were not detected until 4 weeks after RYGB surgery. The basal insulin and C-peptide concentrations were significantly lower than those in diabetic group by 2 weeks after RYGB. Conclusion: The increased insulin sensitivity after RYGB occurs earlier in the liver than in the muscle and both may contribute to long-term remission of type 2 diabetes. Reduced lipid content of hepatocytes and skeletal muscle cells after RYGB may contribute to the improved insulin sensitivity in these cells. (C) 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.