CGMP-independent anti-apoptotic effect of nitric oxide on thapsigargin-induced apoptosis in the pancreatic β-cell line INS-1

Abstract

Aims Low concentrations of nitric oxide (NO) produced by constitutive NO synthase (cNOS) in pancreatic β-cells have been suggested to be a physiological regulator of insulin secretion. In contrast, excessive NO produced by inducible NO synthase is known to mediate β-cell apoptosis. The aim of the present study was to investigate the effect of low concentrations of NO on β-cell apoptosis. Main methods Apoptosis of the pancreatic β-cell line INS-1 was quantitatively determined by Annexin V flow cytometry. Key findings The 24-h incubation with 1 mM DETA/NO, a long half-life NO donor, induced β-cell apoptosis, which was insensitive to the soluble guanylate cyclase (sGC) inhibitor ODQ. In contrast, DETA/NO at lower concentrations until 300 μM concentration-dependently decreased the apoptosis induced by thapsigargin, an inhibitor of endoplasmic reticulum Ca 2+-ATPase. ODQ did not affect the anti-apoptotic effect of DETA/NO. Moreover, neither the cGMP analogue 8-Br-cGMP nor the sGC activator YC-1 mimicked the anti-apoptotic effect of DETA/NO. Significance These results suggest that low levels of NO protect β-cells from thapsigargin-induced apoptosis in a cGMP-independent manner.