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

Sustained high concentration of glucose has been verified toxic to β-cells. Glucose augments Ca(2+)-stimulated insulin release in pancreatic β-cells, but chronic high concentration of glucose could induce a sustained level of Ca(2+) in β-cells, which leads to cell apoptosis. However, the mechanism of high glucose-induced β-cell apoptosis remains unclear. In this study, we use a calcium channel blocker, nifedipine, to investigate whether the inhibition of intracellular Ca(2+) concentration could protect β-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 β-cells apoptosis at least through the endoplasmic reticulum stress pathway and 10 μM nifedipine inhibited Ca(2+) release to protect β-cells from high glucose-induced endoplasmic reticulum stress and apoptosis. These results indicated that inhibition of Ca(2+) over-accumulation might provide benefit to attenuate islet β-cell decompensation in a high glucose environment.