Nifedipine Protects INS-1 β-Cell from High Glucose-Induced ER Stress and Apoptosis

Sustained high concentration of glucose has been verified toxic to beta-cells. Glucose augments Ca2+-stimulated insulin release in pancreatic beta-cells, but chronic high concentration of glucose could induce a sustained level of Ca2+ in beta-cells, which leads to cell apoptosis. However, the mechanism of high glucose-induced beta-cell apoptosis remains unclear. In this study, we use a calcium channel blocker, nifedipine, to investigate whether the inhibition of intracellular Ca2+ concentration could protect beta-cells from chronic high glucose-induced apoptosis. It was found that in a concentration of 33.3 mM, chronic stimulation of glucose could induce INS-1 beta-cells apoptosis at least through the endoplasmic reticulum stress pathway and 10 mu M nifedipine inhibited Ca2+ release to protect beta-cells from high glucose-induced endoplasmic reticulum stress and apoptosis. These results indicated that inhibition of Ca2+ over-accumulation might provide benefit to attenuate islet beta-cell decompensation in a high glucose environment.