Effect of electrical stimulation combined with diet therapy on insulin resistance via mTOR signaling.

Abstract

Insulin resistance (IR) is the impaired insulin response that causes decreased glucose tolerance. Electrical stimulation (ES) can improve insulin sensitivity in the skeletal muscle. However, the underlying molecular mechanisms remain to be elucidated. In the present study, the effect of ES and diet therapy on IR and the role of the mammalian target of rapamycin (mTOR) pathway in the improvement of IR by ES were investigated. A total of 70 Sprague-Dawley male rats were divided into five groups: Normal (n=10), IR control (n=15), diet (n=15), ES (n=15) and ES + diet (n=15) groups. An IR rat model was established by high-fat and high-carbohydrate diet for 5 weeks and confirmed by measurement of fasting plasma glucose (FPG), insulin, insulin sensitivity index (ISI) and IR index. ES on the Zusanli (ST36), Sanyinjiao (SP 6) and Weiwanxiashu (EX-B3) acupoints and the low-fat and low-carbohydrate diet demonstrated protective effects. The body weight, concentrations of FPG, insulin, triglycerides (TG), free fatty acids (FFA) and total cholesterol (TC) of the rats were detected. Pathologic changes in the liver and pancreatic tissues were assessed. Western blotting and immunohistochemistry were performed to determine the role of PI3K/Akt/mTOR signaling. Results demonstrated that ES and diet therapy significantly increased ISI and reduced FPG, IR index, FFA, TG, TC and weight. Inflammatory cell infiltration in the liver and pancreatic tissues was ameliorated and lipid droplets and cavitation in hepatocyte were decreased after ES and diet therapy. The administration of ES and diet therapy also enhanced glucose transport by the upregulation of glucose transporter 4 and accelerated glycogen synthesis through the suppression of glycogen synthase kinase 3α/β via PI3K/Akt/mTOR signaling. Hence, the present results demonstrated that ES combined with diet therapy improved IR through PI3K/Akt/mTOR signaling. The proposed therapy was superior to the method of diet alone.