Preservation of insulin secretory responses to p2-purinoceptor
agonists in zucker diabetic fatty rats.
Tang, Jiping, William Pugh, Kenneth S. Polonsky, and He Zhang.
Section of Endocrinology, Department of Medicine, and Department of
Surgery, The University of Chicago, Chicago, Illinois 60637
APStracts 2:0207E, 1995.
The role of P2-purinoceptor agonists in regulatory of insulin
secretion in Zucker diabetic fatty (ZDF) rats was studied using the
isolated perfused pancreas and [Ca2+]i microfluorimetry. The relative
potency of different purinoceptor agonists to stimulate the insulin
secretory process was consistent with the conclusion that responses
in [Ca2+]i and insulin secretion are mediated by the P2y-subtype of
purinoceptors. Additional studies using specific antagonists of the
Ca2+ signalling pathway indicated that activation of P2y-purinoceptor
releases Ca2+ from intracellular stores and promotes Ca2+ entry
through voltage-independent (VICC) rather than voltage-dependent Ca2+
channels (VDCC) on the [beta]-cell membrane. Perfused pancreas and
isolated islets from ZDF rats demonstrated markedly reduced or absent
insulin secretion and [Ca2+]i responses to glucose and KCl. In
contract, responses to P2y-purinoceptor agonists were normal
indicating that the secretion coupling pathway activated by these
agonists is preserved in glucose-unresponsive islets from diabetic
animals. These observations raise the possibility that the
purinoceptor pathway may play an important role in regulating insulin
secretion in hyperinsulinemic non-insulin dependent diabetes (NIDDM).
Received 8 August 1995; accepted in final form 27 September 1995.
APS Manuscript Number E376-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95