Phosphoinositide Metabolism and Insulin Secretion

to respond to extracellular stimulation with a rapid increase in phosphatidylinositol turnover, the present studies were undertaken to determine whether carbohydrate-stimulated insulin secretion from the isolated rat pancreatic islet is accompanied by detectable alterations in the phosphatidylinositol metabolism of this tissue. We have demonstrated that rat pancreatic islets incubated with tritiated myo-inositol rapidly incorporate radioactivity into islet phosphatidylinositol. Incubation of prelabeled islets with elevated concentrations of carbohydrates which stimulate insulin scretion (D-glucose -and D-mannose) results in a decrease in the recovery of lipidbound radioactivity, whereas incubation with carbohydrates which do not stimulate insulin secretion (D-galactose and myo-inositol) has no effect upon the recovery of lipid-bound radioactivity. Within 2 min of exposure of prelabeled islets to elevated concentrations of D-glucose, a decrease in the recovery of [2-'H]myo-inositolderived radioactivity in islet phosphatidylinositol can be demonstrated. When islets prelabeled with [2-8H]myoinositol are perifused with elevated concentrations of D-glucose or D-mannose (but not D-galactose or myoinositol) a rapid and transient increase in the rate of extracellular release of water-soluble radioactivity is observed. Since a significant fraction of the radioactivity released under these conditions is in the form of myoinositol-phosphate, cyclic myo-inositol-1,2-phosphate, and glycerophosphorylmyo-inositol, it is presumably derived This work was presented in part at the Joint Annual Meetings of the Southern Section of The American Federation for Clinical Research, The Southern Society for Clinical Investigation, and The Southern Society for Pediatric Research, New Orleans, La., 1 February 1975 (Clin. Res. 23: 10A, 1975). Received for publication 5 August 1975 and in revised form 17 November 1975. from the cleavage of labeled islet phosphatidylinositol. It is speculated that alterations in the metabolism of myoinositol-containing phospholipids may have a functional role in the process of insulin secretion from the pancreatic beta cell.