Ganglionic and cholinergic versus direct islet insulinotropic
effect of gastrin releasing peptide in the mouse.
Karlsson, Sven, Frank Sundler, and Bo Ahr[acute]en.
Department of Medicine, Lund University, Malm[diaeresis]o
University Hospital and Department of Physiology and Neuroscience,
Section of Neuroendocrine Cell Biology, Lund University, Sweden
APStracts 4:0209E, 1997.
Gastrin releasing peptide (GRP) stimulates insulin secretion by a
direct islet effect. In this study, we initially demonstrated, by
immunocytochemistry of the mouse pancreas, GRP-immunoreactive nerve
fibers within exocrine tissue, islets and intrapancreatic ganglia. A
more pronounced GRP-innervation was found in ganglia compared to in
islets. We therefore studied whether indirect cholinergic mechanisms
contribute to the insulinotropic action of GRP. In mice, the
insulinotropic response to GRP (4.25 nmol/kg, iv) was inhibited by
the m3-selective, muscarinic receptor antagonist 4-DAMP (0.21 mol/kg;
by 68 %, P<0.05) and by the ganglionic blocker, hexamethonium (28
mol/kg; by 98%, P<0.05). In contrast, in isolated islets, 4-DAMP or
hexamethonium (10 or 100 [mu]M) did not inhibit GRP (100 nM)-induced
insulin secretion. Furthermore, afferent denervation by neonatal
capsaicin did not affect the insulin response to GRP. We conclude
that the insulinotropic effect of GRP in the mouse is mediated by
both direct islet effects and through activation, at the ganglionic
level, of postganglionic cholinergic nerves. In vivo the indirect
cholinergic mechanism predominates.
Received 18 November 1996; accepted in final form 18 September
1997.
APS Manuscript Number E577-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997