Gypenosides modulate NCX calcium flux, insulin secretion and cytoprotection in BRIN-BD11 pancreatic β-cells

Gypenosides are saponins extracted from the plant Gynostemma pentaphyllum, suggested to have antidiabetic and anti-obesity potential. However, its mechanism of action is not fully understood. The present study aimed to investigate the cytoprotective and insulin stimulatory effects of gypenosides using the rat BRIN-BD11 {beta}-cell line. Gypenosides provided a significant cytoprotective effect against palmitate-, peroxide- and cytokine-induced cytotoxicity, with upregulation of antioxidant genes Nrf2, Cat, Sod1, and Gpx1. Acutely, gypenosides enhanced intracellular calcium ([Ca2+]i) and insulin secretion in a dose-dependent manner. The presence of the sodium/calcium exchanger (NCX) reverse mode inhibitor SN-6 blocked the gypenosides mediated increase in [Ca2+]I but not the insulin secretion. These findings indicate that gypenosides may enhance [Ca2+]i by activating the reverse mode of NCX channels and a possible calcium-independent mechanism involved in their insulin secretion. Gypenosides also upregulate the antioxidant gene expression and protect against oxidative stress and lipotoxicity, providing the rationale for their observed antidiabetic actions.