AJP - Endocrinology and Metabolism, Vol 272, Issue 4 E671-E677, Copyright © 1997 by American Physiological Society

ARTICLES

Regulation of insulin secretion via ATP-sensitive K+ channel independent mechanisms: role of phospholipase C

W. S. Zawalich and K. C. Zawalich
Yale University School of Nursing, New Haven, Connecticut 06536-0740, USA.

Groups of rat or mouse islets were isolated and perifused with 20 mM glucose plus 200 microM diazoxide. The further addition of 30 mM K+ resulted in a rapid and sustained biphasic insulin secretory response. The onset of secretion in response to the addition of K+ was comparable in both species, but the magnitude of the response was significantly greater from rat islets. After the labeling of islet phosphoinositide pools with 2-[3H]inositol, the accumulation of labeled inositol phosphates (IP) in response to 30 mM K+ addition in the simultaneous presence of 20 mM glucose plus diazoxide was assessed. The addition of 30 mM K+ significantly increased IP accumulation approximately 300% in rat islets, whereas only an insignificant 25-30% increase was observed in mouse islets. The protein kinase C inhibitor staurosporine (50 nM) dramatically reduced the sustained secretory response from rat islets in the presence of 30 mM K+, 20 mM glucose, and diazoxide. Its effect was minimal on mouse islets and a significant inhibitory effect on insulin secretion was observed only during the final 5 min of the perifusion. The further addition of carbachol, an agonist that activates an isozyme of phospholipase C distinct from that activated by glucose, together with K+, 20 mM glucose, plus diazoxide resulted in a sustained amplification of insulin secretion from mouse but not rat islets. K+ (30 mM)-induced insulin secretion in the presence of 3 mM glucose was similar from perifused rat or mouse islets, a finding that would seem to preclude the activation of voltage-regulated Ca2+ channels as the pertinent difference. These results confirm previous observations with these species and document another anomaly that exists between the responses of rat islets compared with mouse islets. The inability to activate a nutrient- and calcium-regulated phospholipase C isozyme in mouse islets to the same extent as in rat islets appears to account, at least in part, for these different insulin secretory responses under these unique conditions.

This article has been cited by other articles:

				W. S. Zawalich, K. C. Zawalich, G. J. Tesz, J. A. Sterpka, and W. M. Philbrick Insulin secretion and IP levels in two distant lineages of the genus Mus: comparisons with rat islets Am J Physiol Endocrinol Metab, May 1, 2001; 280(5): E720 - E728. [Abstract] [Full Text] [PDF]

				R. Lemmens, O. Larsson, P.-O. Berggren, and MS Islam Ca2+-induced Ca2+ Release from the Endoplasmic Reticulum Amplifies the Ca2+ Signal Mediated by Activation of Voltage-gated L-type Ca2+ Channels in Pancreatic beta -Cells J. Biol. Chem., March 30, 2001; 276(13): 9971 - 9977. [Abstract] [Full Text] [PDF]