Objective To investigate the effects of Roux-en-Y gastric bypass (RYGB) on hepatic and peripheral insulin sensitivity in rats with type 2 diabetes and their possible mechanisms.Methods 5-6 week old SPF male Sprague-Dawley rats were divided into 2 groups: diabetic RYGB group (n=21) and diabetic RYGB sham group (n=7).The hyperinsulinemic-euglycemic clamp with tracer infusion was completed at 2,4,and 8 weeks postoperatively to assess the 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 RYGB had a profound effect on the plasma lipid profile.Two weeks after surgery,the hepatic insulin sensitivity index was significantly improved and the hepatic triglyceride was decreased in the RYGB group (P<0.05).The significant increased insulin sensitivity was not detected until four weeks after RYGB surgery,the M value was significantly increased and the TG content in the muscle tissue was significantly decreased (P<0.05).Conclusions The increased insulin sensitivity after RYGB occurs earlier in the liver than in the muscle and both may contribute to the long-term remission of type 2 diabetes.Reduced lipid content in hepatocytes and skeletal muscle cells after RYGB may contribute to the improved insulin sensitivity in these cells.

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 hyperinsulinemiceuglycemic 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.

Objective To explore the effects of Roux-en-Y gastric bypass (RYGB) on hepatic autophagy in obese diabetic rats.Methods Sprague-Dawley diabetes rats were randomly divided into three groups:diabetic group(n =8),diabetic sham RYGB group (n =8) and diabetic RYGB group (n =8).Hyperinsulinemic-euglycemic clamps with tracer infusion were completed to assess insulin sensitivity (IS).Triglyceride (TG) levels in liver tissue were tested.The protein expression levels of P62 (sequestosome 1)and the conversion of LC3 (microtubule-associatedprotein 1 light chain 3) in liver were detected by Western blot.The concentration of glucagon-like peptide-1 (GLP-1) in plasma was detected by ELISA and the correlation between GLP-1 and autophagy was analyzed in 2 weeks after operation.Results In comparison with diabetic and diabetic sham RYGB groups,IS increased by 63％ (F =10.87,P ＜ 0.01) and TG content decreased by 91％ (F =146.3,P ＜ 0.01) in the liver in RYGB group.In RYGB group,the conversion of LC3-Ⅰ to LC3-Ⅱ raised(F =17.01,P ＜ 0.01),the protein expression of P62 decreased(F =19.77,P ＜0.01) and the concentration of GLP-1 in plasma increased by 90％ (F =112.8,P ＜ 0.01).The marked increase of autophagy in liver after RYGB correlated with the plasma GLP-1 level (r2 =0.66,P =0.014 3)Conclusions RYGB reduces hepatic lipid toxicity and improves lipid metabolism disorder by increasing autophagy,increased GLP-1 secretion after RYGB may be one of the reasons for activating autophagy.