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

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.