Regulation of glucose dynamics by noninvasive peripheral electrical stimulation in normal and insulin-resistant rats

Background. The epidemic nature of type 2 diabetes mellitus (T2DM), along with the downsides of current treatments, has raised the need for therapeutic alternatives. Methods. We studied normo-glycemic and high-fat diet (HFD), induced insulin-resistant Wistar Han rats for 2 to 3 weeks. Rats received peripheral electrical stimulation (PES) treatment (2 Hz/16 Hz bursts, 10 mA) in their hind limbs for 3 min, 3 times per week. Glucose tolerance was evaluated by using a glucose tolerance test at the beginning and again at the end of the study. The effect of an acute PES treatment on metabolic rates of glucose appearance and turnover was measured by using the hyperinsulinemic-euglycemic clamp (HEGC) test. Results. Repeated PES treatment significantly inhibited the progression of glucose intolerance in normal and insulin-resistant rats and prevented HFD-induced gains in body weight and fat mass. Acute treatment induced a prolonged effect on glucose turnover, as evaluated by the HEGC test. Increased hepatic glucose output was observed during the basal state (P < 0.005). Under hyperinsulinemic conditions, PES improved tissue sensitivity to insulin (41.1%, P < 0.01), improved suppression of hepatic glucose production (58.9 +/- 4.4% vs. 87.1 +/- 4.4%, P < 0.02) and significantly elevated the rate of glycogenesis (P < 0.01), compared with controls. Conclusions. The present study indicates that a noninvasive PES treatment of very short duration is sufficiently potent to stimulate glucose utilization and improve hepatic insulin sensitivity in rats. Repeated PES treatment may have a beneficial effect on HFD-induced adiposity and control of body weight. (C) 2016 Elsevier Inc. All rights reserved.