Role of low-voltage-activated (LVA) calcium channels in basal insulin secretion

The underlying mechanisms of basal insulin secretion in pancreatic β-cells have not been elucidated. We used rat and mouse β-cells as models to show that LVA Ca²⁺ channels, under non-stimulatory conditions, mediates Ca²⁺ influx which initiates insulin secretion. Previous studies show that LVA Ca²⁺ channels participates in the Ca²⁺ influx induced by 30 mM KCl, we have demonstrated that NiCl₂, a selective LVA Ca²⁺ channel antagonist in β-cells, blocked cytokine-enhanced basal free Ca²⁺ levels under non-stimulatory conditions (3.3 mM glucose and 4.7 mM KCl in bath solution). Direct measurements of basal insulin secretion by radioimmunoassay showed that both NiCl₂ and mibefradil suppressed basal insulin secretion in isolated rat islets and in NIT-1 cells, a mouse insulin-secreting cell line that constitutively expresses LVA Ca²⁺ currents. 10 μM NiCl₂ also blocked the increased basal insulin secretion in cytokine-treated mouse islets (25 U/ml interleukin-1β and 300 U/ml interferon-γ) whereas in non-treated islets, NiCl₂ exerted no effect on secretion. These results suggest that LVA Ca²⁺ channels play an important role in the regulation of basal cytoplasmic Ca²⁺ concentration and basal insulin secretion. This work was supported by Faculty Development Award from the PhRMA Foundation and the Career Development Award from the American Diabetes Association to M. Li.