A low voltage-activated Ca2+ current mediates cytokine-induced pancreatic β-cell death

Abstract

Insulin-dependent diabetes mellitus is characterized by the selective destruction of pancreatic β-cells. Chronic treatment with cytokines induced a low voltage-activated (LVA) Ca2+ current in mouse β-cells. The concomitant increase in the basal cytoplasmic free Ca2+ concentration ([Ca2+](i)) was associated with DNA fragmentation and cell death. Antagonists of LVA Ca2+ channels prevented this elevation of basal [Ca2+](i) and DNA fragmentation and reduced the percentage of cell death. Exposure to cytokines did not affect the profile of Ca2+ currents or basal [Ca2+ ](i) in glucagon-secreting α-cells. An increased Ca2+ signal through LVA Ca2+ channels may thus be a key feature in cytokine-induced β- cell destruction.