Arsenite and its metabolite, methylarsonite, inhibit calcium influx during glucose-stimulated insulin secretion in pancreatic islets

摘要

Numerous epidemiological studies have shown significant associations between chronic exposure to arsenic (As) and an increased risk of diabetes. However, the molecular mechanisms underlying the diabetogenic effects of As exposure have not been sufficiently studied. Previous studies published by our laboratory have shown that inorganic As (iAs) and its trivalent methylated metabolites inhibit Glucose- Stimulated Insulin Secretion (GSIS) in isolated murine pancreatic islets. Here, we investigate the effects of iAs (arsenite) and one of its metabolite, methylarsonite (MMAs), on calcium influx, one of the key steps in GSIS. Our data suggest that iAs and MMAs inhibit calcium influx after glucose stimulation and that MMAs may be more potent than iAs as an inhibitor of this process. Further studies using isolated islets and β-cell lines are warranted to confirm these observations and to identify the molecular targets of iAs and MMAs.