Insulin release transduction mechanism through acid glucan-1, 4 -[alpha]-glucosidase activation is ca2+-regulated. Salehi, Albert, Henrik Mos[acute]en, and Ingmar Lundquist. Department of Pharmacology, University of Lund, Lund, Sweden
APStracts 4:0269E, 1997.
An important signal involved in glucose-stimulated insulin secretion is transduced through the action of a lysosomal acid glucan-1,4 -[alpha]-glucosidase. We investigated the Ca2+-dependency of this enzyme activity in relation to insulin release. In isolated islets increased levels of extracellular Ca2+ induced a large increase in acid glucan-1,4-[alpha]-glucosidase activity accompanied by a similar increase in insulin release both at substimulatory and stimulatory concentrations of glucose. At low glucose the Ca2+- "inflow" blocker nifedipine unexpectedly stimulated enzyme activity without affecting insulin release. However, nifedipine suppressed 45Ca2+- outflow from perifused islets at low glucose and at Ca2+-deficiency when intracellular Ca2+ was mobilized by carbachol. This nifedepine -induced retention of Ca2+ was reflected in increased acid glucan-1,4 -[alpha]-glucosidase activity. Adding different physiological Ca2+ -concentrations or nifedipine to islet homogenates did not increase enzyme activity. Neither selective glucan-1,4-[alpha]-glucosidase inhibition nor the ensuing suppression of glucose-induced insulin release was overcome by a maximal Ca2+-concentration. Hence, Ca2+ -induced changes in acid glucan-1,4-[alpha]-glucosidase activity were intimately coupled to similar changes in Ca2+-glucose-induced insulin release. Ca2+ did not affect the enzyme itself but presumably activated either glucan-1,4-[alpha]-glucosidase-containing organelles or closely interconnected messengers. 

Received 12 June 1997; accepted in final form 24 November 1997.
APS Manuscript Number E276-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 December 1997