AJP - Endocrinology and Metabolism, Vol 270, Issue 3 E504-E512, Copyright © 1996 by American Physiological Society
Preservation of insulin secretory responses to P2 purinoceptor agonists in Zucker diabetic fatty rats
J. Tang, W. Pugh, K. S. Polonsky and H. Zhang
Department of Medicine, The University of Chicago, Illinois 06037, USA.
The role of P2 purinoceptor agonists in regulatory insulin secretion in
Zucker diabetic fatty (ZDF) rats was studied using the isolated perfused
pancreas and intracellular Ca2+ concentration ([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+
signaling pathway indicated that activation of P2y purinoceptor releases
Ca2+ from intracellular stores and promotes Ca2+ entry through
voltage-independent rather than voltage-dependent Ca2+ channels 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 contrast, 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 mellitus.
