Subcellular localization of the alterations in phosphatidylinositol metabolism following glucose-induced insulin release from rat pancreatic islets.

The subcellular localization of the incorporation of 2-(3H)-myoinositol into lipids has been studied in isolated pancreatic islets of the rat. The recovery of lipid-bound myoinositol increased with time in the nuclear, mitochondrial, microsomal, and secretory granule fractions. The utilization of a filtration technique for the more complete separation of mitochondrial and secretory granule elements permitted us to show that the recovery of lipid-bound 2-(3H)-myoinositol increased most rapidly in the secretory granule fraction. A 30-minute exposure of prelabeled islets to a stimulatory concentration of D-glucose (3.0 mg./ml.) resulted in a statistically significant decrease in the amount of lipid-bound 2-(3H)-myoinositol that was recovered from the secretory granule fraction (p less than 0.001). In contrast, exposure of islets to the elevated glucose concentration had no statistically significant effect on the recovery of lipid-bound radioactivity from other subcellular fractions. Since the majority of lipid-bound radioactivity associated with the secretory granule fraction could be recovered with the presumptive secretory granule membranes, these data suggest that the hydrolysis of phosphatidylinositol that accompanies glucose-induced insulin secretion from the rat pancreatic islet may be localized to the beta granule and, in particular, to its limiting membrane.