The digitonin-permeabilized pancreatic islet model. Effect of myo-inositol 1,4,5-trisphosphate on Ca2+ mobilization

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Abstract
Glucose-induced insulin secretion is thought to be mediated by submicromolar increases in intracellular Ca2+, although the intracellular processes are not well understood. The previously characterized digitonin-permeabilized insulin-secreting rat pancreatic islet model was used to study the role of myo-inositol-1,4,5-trisphosphate (IP3), a putative second messenger for mobilization of intracellular Ca2+, Ca2+ efflux from the endoplasmic reticulum was studied with or without vanadate present to inhibit Ca2+ reuptake. IP3 (10 .mu.M), at a free Ca2+ level of 0.06 .mu.M, increased Ca2+ release by 30% and, when vanadate was present, by 50%. Maximal and half-maximal Ca2+ release was observed at 10 .mu.M- and 2.5 .mu.M-IP3, respectively. IP3 provoked a rapid release that was followed by slow reuptake. Reuptake was diminished in the presence of vanadate. Inositol-1,4-bisphosphate, inositol-1-phosphate and other phosphoinositide metabolites did not have any significant effect. Because increases in Ca2+ levels in the submicromolar range induce insulin release in digitonin-permeabilized islets, the results are consistent with the concept of IP3 serving as a 2nd messenger for insulin secretion.