Vagal Nerve Stimulation for Glycemic Control in a Rodent Model of Type 2 Diabetes.

Abstract

Vagal nerve stimulation (VNS) has been reported to reduce body weight and improve sympathovagal imbalance in both basic and clinical studies. Its effects on glycemic control were however unclear. The aims of this study were to investigate the effects of VNS with various parameters on blood glucose and its possible mechanisms in rats. A hyperglycemic rodent model induced by glucagon was used initially to optimize the VNS parameters; then, a type 2 diabetic rodent model induced by high-fat diet combined with streptozotocin was used to validate the VNS method. The VNS electrodes were implanted at the dorsal subdiaphragmatic vagus; three subcutaneous electrodes were implanted at the chest area for recording electrocardiogram in rats induced by glucagon. (1) VNS with short pulse width of 0.3ms but not 3ms reduced blood glucose during an oral glucose tolerance test (OGTT), with a 38.4% reduction at 15min and 26.9% at 30min (P < 0.05, vs. sham-VNS respectively). (2) VNS at low frequency of 5Hz but not 14Hz or 40Hz reduced blood glucose during the OGTT (P < 0.05, vs. sham-VNS). (3) Intermittent VNS was more potent than continuous VNS (P < 0.01). (4) No difference was found between unilateral VNS and bilateral VNS. (5) VNS enhanced vagal activity (P = 0.005). (6) The hypoglycemic effect of VNS was blocked by glucagon-like peptide-1 (GLP-1) antagonist exendin-4. VNS at 5Hz reduces blood glucose in diabetic rats by enhancing vagal efferent activity and the release of GLP-1.