Electroacupuncture plus metformin lowers glucose levels and facilitates insulin sensitivity by activating MAPK in steroid-induced insulin-resistant rats

Background Type 2 diabetes mellitus is the predominant form of diabetes. Although metformin is the preferred first-line drug for treatment of the disease, it is associated with a risk of secondary failure. Electroacupuncture (EA) can enhance insulin sensitivity and reduce blood glucose levels. Objectives To examine, in an animal study, whether EA combined with metformin (EA-metformin) results in a better glucose-lowering effect and greater insulin sensitivity than metformin alone in steroid-induced insulin-resistant rats. Methods Adult Wistar rats were injected with dexamethasone to induce diabetes and subsequently treated with EA plus metformin or metformin alone. Variations in plasma glucose, plasma insulin, and plasma free fatty acid levels were studied at the midpoint and end of the experimental course. Insulin receptor substrate 1 (IRS-1) and peroxisome proliferator-activated receptor gamma (PPAR-gamma), which are associated with glucose transporter type 4 (GLUT4) translocation, and mitogen-activated protein kinase (MAPK), which is related to GLUT4 activation, were measured after EA treatment. Results We found that EA-metformin resulted in a better glucose-lowering effect, greater insulin sensitivity, lower plasma free fatty acid levels and higher levels of MAPK than metformin alone (p<0.05). There were no significant differences between treatment groups in expression of IRS-1 or PPAR-gamma. Conclusions The glucose-lowering effect and increased insulin sensitivity associated with EA-metformin administration is governed, at least in part, by its ability to stimulate the activation of GLUT4 via upregulation of MAPK expression.