AJP - Endocrinology and Metabolism, Vol 269, Issue 3 E575-E582, Copyright © 1995 by American Physiological Society

ARTICLES

Synergistic interaction of glucose and neurohumoral agonists to stimulate islet phosphoinositide hydrolysis

G. G. Kelley, K. C. Zawalich and W. S. Zawalich
Department of Internal Medicine, Yale University School of Medicine, New Haven 06520-8020, USA.

The interaction between neurohumoral agonists and glucose to stimulate phosphoinositide (PI)-specific phospholipase C (PLC) and insulin release was examined. In freshly isolated rat islets, maximal glucose (40 mM), cholecystokinin (CCK; 300 nM), or carbachol (CCh; 1 mM) stimulated PI hydrolysis 6.5-, 9.8-, and 5.7-fold, respectively, above basal. The combination of glucose and CCK or of glucose and CCh, but not of CCK and CCh, synergistically increased PI hydrolysis 23.2- and 21.6-fold, respectively, indicating that these secretagogues activate PLC by distinct pathways and that there is an interaction between them. This synergy was maximal at physiological concentrations of stimulatory glucose (8-10 mM) and was paralleled by a marked synergistic stimulation of insulin secretion. The enhanced PI response was partially Ca2+ dependent and may involve the activation of distinct isozymes of PLC, which we identify in islets. These studies demonstrate for the first time a unique and highly sensitive synergistic interaction between glucose and neurohumoral agonists to stimulate PI hydrolysis, and they suggest that enhanced PI hydrolysis is important in the potentiation of glucose- and neurohumoral-stimulated insulin secretion.

This article has been cited by other articles:

				H. Yamazaki, K. C. Zawalich, and W. S. Zawalich Desensitization of the pancreatic beta-cell: effects of sustained physiological hyperglycemia and potassium Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): H1381 - H1387. [Abstract] [Full Text] [PDF]

				F. Ferreira, E. Filiputti, V. C. Arantes, L. F. Stoppiglia, E. P. Araujo, V. Delghingaro-Augusto, M. Q. Latorraca, M. H. Toyama, A. C. Boschero, and E. M. Carneiro Decreased Cholinergic Stimulation of Insulin Secretion by Islets from Rats Fed a Low Protein Diet Is Associated with Reduced Protein Kinase C{alpha} Expression J. Nutr., March 1, 2003; 133(3): 695 - 699. [Abstract] [Full Text] [PDF]

				W. S. Zawalich, M. Bonnet-Eymard, and K. C. Zawalich Glucose-induced desensitization of the pancreatic beta -cell is species dependent Am J Physiol Endocrinol Metab, December 1, 1998; 275(6): E917 - E924. [Abstract] [Full Text] [PDF]

				W. S. Zawalich, M. Bonnet-Eymard, K. C. Zawalich, and G. C. Yaney Chronic exposure to TPA depletes PKCalpha and augments Ca-dependent insulin secretion from cultured rat islets Am J Physiol Cell Physiol, May 1, 1998; 274(5): C1388 - C1396. [Abstract] [Full Text] [PDF]

				W. Muller, U. Heinemann, and K. Berlin Cholecystokinin Activates CCKB-Receptor-Mediated Ca-Signaling in Hippocampal Astrocytes J Neurophysiol, October 1, 1997; 78(4): 1997 - 2001. [Abstract] [Full Text] [PDF]