Nitric oxide donor sin-1 inhibits insulin release by differentially
suppressing [beta]-cell stimulus-secretion coupling.
Sj[diaeresis]oholm, [angstrom]ake.
Department of Molecular Medicine, The Endocrine and Diabetes Unit,
The Rolf Luft Center for Diabetes Research, Karolinska Institute,
Karolinska Hospital (L6:01B), S-171 76 Stockholm, Sweden
APStracts 3:0150C, 1996.
Preceding the onset of insulin-dependent diabetes mellitus, pancreatic
islets are infiltrated by macrophages secreting interleukin-1[beta]
which exerts cytotoxic and inhibitory actions on islet [beta]-cell
insulin secretion through induction of nitric oxide (NO) synthesis.
The influence of the NO donor 3-morpholino-sydnonimine (SIN-1) on
insulin secretion from isolated pancreatic islets in response to
various secretagogues was investigated. Stimulation of insulin
release evoked by glucose, phospholipase C activation with carbachol
and protein kinase C activation with phorbol ester was obtunded by
SIN-1, whereas the response to adenylyl cyclase activation or K+
-induced depolarization was not affected. It is concluded that enzymes
involved in glucose catabolism, phospholipase C, or protein kinase C
may be targeted by NO. Reversal of SIN-1 inhibition of glucose
-stimulated insulin release by dithiothreitol suggests that NO may
inhibit insulin secretion partly by S-nitrosylation of thiol
residues in key proteins in the stimulus-secretion coupling. These
adverse effects of NO on the [beta]-cell stimulus-secretion coupling
may be of importance for the development of the impaired insulin
secretion characterizing diabetes mellitus.
Received 10 January 1996; accepted in final form 26 April 1996.
APS Manuscript Number C12-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 May 96