The digitonin-permeabilized pancreatic islet model. Effect of myo-inositol 1,4,5-trisphosphate on Ca super(2+) mobilization

Glucose-induced insulin secretion is thought to be mediated by submicromolar increases in intracellular Ca super(2+), although the intracellular processes are not well understood. The authors have used the previously characterized digitonin-permeabilized insulin-secreting pancreatic islet model to study the role of myo-inositol 1,4,5-trisphosphate (IP sub(3)), a putative second messenger for mobilization of intracellular Ca super(2+), Ca super(2+) efflux from the endoplasmic reticulum was studied with or without vanadate present to inhibit Ca super(2+) reuptake. IP sub(3) (10 mu M), at a free Ca super(2+) level of 0.06 mu M, increased Ca super(2+) release by 30% and, when vanadate was present, by 50%. Maximal and half maximal Ca super(2+) release was observed at 10 mu M- and 2.5 mu m-IP sub(3), respectively.