Effects of secretagogues on insulin biosynthesis and secretion in
polyamine-depleted pancreatic [beta]-cells.
Sjoholm, Ake.
Department of Internal Medicine,
L[diaeresis]owenstr[diaeresis]omska Hospital, S-194 89 Upplands
V[umlaut]asby, Sweden
APStracts 2:0379C, 1995.
To extend previous observations on the importance of polyamines for
glucose-stimulated insulinogenesis [Welsh, N., and [angstrom]a.
Sj[diaeresis]oholm. Polyamines and insulin production in isolated
mouse pancreatic islets. Biochem. J. 252: 701-707, 1988], the impact
of other secretagogues on insulin secretion of islets partially
depleted in polyamines by selective inhibitors of L-ornithine
decarboxylase and S-adenosyl-L-methionine decarboxylase was
monitored. It was found that glucose-sensitive, but not basal,
insulin release was partially abolished in polyamine-deficient
islets. Qualitatively similar impairments in insulin secretion were
recorded when such islets were stimulated with non-glucidic nutrients
(a-ketoisocaproic acid + L-glutamine), a cationic amino acid (L
-arginine), activators of phospholipase C (carbachol) or protein
kinase C (12-O-tetradecanoylphorbol 13-acetate), a cyclic AMP-raising
agent (forskolin), or a hypoglycemic sulfonylurea (glibenclamide).
Additionally, glucose-responsive (pro)insulin biosynthesis was
preferentially impeded in polyamine-deficient islets. It is concluded
that polyamines act as permissive or stimulatory factors in insulin
production and release. In addition, they seemingly do not act
inhibitory on phospholipase C, protein kinase C or Ca2+ influx in
these islets, contrasting to reports using insulinoma and other
cells.
Received 27 July 1995; accepted in final form 10 October 1995.
APS Manuscript Number C461-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95