Species differences in glucose-induced biphasic insulin secretion, glucose-induced time-dependent potentiation and glucose-induced time -dependent suppression : role of information flow in the phospholipase c/protein kinase c signaling pathway. Zawalich, Walter S., Kathleen C. Zawalich. Yale University School of Nursing, 100 Church Street South, P.O. Box 9740, New Haven, CT 06536-0740, 203-785-5522(Tel), 203-785 -6455(Fax)
APStracts 3:0122E, 1996.
Biphasic insulin secretion in response to a sustained glucose stimulus occurs when rat or human islets are exposed to high levels of the hexose. A transient burst of hormone secretion is followed by a rising and sustained secretory response that in the perfused rat pancreas is 25-75 fold greater that prestimulatory insulin release rates. This insulin secretory response is paralleled by a significant 5-6 fold increase in the phospholipase C (PLC)-mediated hydrolysis of islet phosphoinositide (PI) pools by high glucose. In contrast, mouse islets when stimulated under comparable conditions with high glucose display a second phase response that is flat and only slightly (2-3 fold) greater that prestimulatory release rates. The minimal second phase insulin secretory response to high glucose is accompanied by the minimal activation of PLC in mouse islets as well. However, stimulation of mouse islets with the protein kinase C (PKC) activator tetradecanoyl phorbol acetate (TPA) or the muscarinic agonist carbachol, which significantly activates an isozyme of PLC distinct from that activated by high glucose, induces a rising and sustained second phase insulin secretory response. When previously exposed to high glucose both rat and human islets respond to subsequent restimulation with an amplified insulin secretory response. They display priming, sensitization or time dependent potentiation. In contrast, mouse islets primed under similar conditions with high glucose fail to display this amplified insulin secretory response upon restimulation. Mouse islets can, however, be primed by brief exposure to either TPA or carbachol. Finally, while rat islets are desensitized by chronic exposure to high glucose, mouse islet insulin secretory responses are relatively immune to this adverse effect of the hexose. These and other findings are discussed in relationship to the role being played by agonist-induced increases in the PLC -mediated hydrolysis of islet phosphoinositide pools and the activation of protein kinase C in these species- specific insulin secretory response patterns. 

Received 30 March 1996; accepted in final form 4 June 1996.
APS Manuscript Number E158-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96