Mechanisms of amelioration in hepatic insulin sensitivity after Roux-en-Y gastric bypass surgery in type 2 diabetic rats

Abstract

Objective To investigate the effects of RYGB on hepatic and peripheral insulin sensitivity in type 2 diabetes rats and the mechanisms. Methods Sprague-Dawley rats were divided into 2 groups: diabetic RYGB group (n=10) and diabetic sham RYGB group (n=10). The hyperinsulinemic-euglycemic clamp with tracer infusion was completed at 2 weeks postoperatively to assess insulin sensitivity. The lipid content in liver tissue was examined. Malondialdehyde (MDA) and superoxide dismutase (SOD) activities in the liver were measured. The protein expressions of PERK and p-PERK in livers were also detected by Western blot. Results RYGB significantly improved hepatic insulin sensitivity index and decreased hepatic triglyceride concentration (P<0.05), without an improvement in peripheral insulin sensitivity. The ratio of MDA to SOD and the protein expression of p-PERK in the livers were lower in the RYGB group than in the sham RYGB group. Conclusions The increased insulin sensitivity after RYGB occurs earlier in the liver than in the muscle tissue. The amelioration of hepatic tissue lipotoxicity after RYGB decreased the degrees of oxidative stress and endoplasmic reticulum stress, which may contribute to the improved hepatic insulin sensitivity. Key words: Diabetes mellitus, Type 2; Anastomosis, Roux-en-Y; Insulin