Glucose and neurohumoral agonists interact synergistically to stimulate islet phosphoinositide hydrolysis. Kelley, Grant G., Kathleen C. Zawalich, Walter S. Zawalich. Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 -8020, Yale University School of Nursing, 25 Park Street, New Haven, CT 06536-0740
APStracts 2:0073E, 1995.
The interaction between neurohumoral agonists and glucose to stimulate phosphoinositide-specific phospholipase C (PLC) and insulin release was examined. In freshly isolated rat islets, maximal glucose, 40mM, cholecystokinin (CCK), 300nM, or carbachol (CCh), 1mM, stimulated phosphoinositide (PI) hydrolysis 6.5, 9.8, and 5.7 fold above basal respectively. The combination of glucose and CCK, or glucose and CCh, but not CCK and CCh, however, 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 these pathways. This synergy was maximal at physiologic stimulatory glucose concentrations (8-10mM), 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 suggest that enhanced PI hydrolysis is important in the potentiation of glucose and neurohumoral-stimulated insulin secretion. 

Received 9 February 1995; accepted in final form 7 April 1995.
APS Manuscript Number E58-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.