Gymnemic Acid Alleviates Type 2 Diabetes Mellitus and Suppresses Endoplasmic Reticulum Stress in Vivo and in Vitro

Gymnemic acid (GA) is an herbal ingredient that can improve glucose metabolism in patients with diabetes mellitus. In this study, we evaluated the ameliorative effects of GA on insulin resistance (IR) and identified the mechanisms in type 2 diabetes mellitus (T2DM) rats and IR HepG2 cells. GA effectively enhanced glucose uptake in IR HepG2 cells from 11.9 ± 1.09 to 14.7 ± 1.38 mmol/L and lowered fasting blood glucose (blood glucose levels in groups treated with GA at 40 and 80 mg/kg/day were reduced by 15.2% and 26.7%, respectively) and oral glucose tolerance. Both in vivo and in vitro, GA downregulated the expression of endoplasmic reticulum (ER) stress indicator proteins such as ORP150, p-c-Jun, p-PERK, and p-eIF2α. In addition, the improvement of ER stress regulated the insulin signal transduction proteins, reducing p-IRS-1(ser) levels and increasing p-IRS-1(tyr) in GA-treated T2DM rats and IR HepG2 cells. In summary, the mechanism underlying the hypoglycemic effects of GA may be associated with alleviation of ER stress and facilitation of insulin signal transduction in T2DM rats and IR HepG2 cells.