Preservation of insulin secretory responses to P2 purinoceptor agonists in Zucker diabetic fatty rats
Tang, J.; Pugh, W.; Polonsky, K.S.; Zhang, H.
American Journal of Physiology 270(3 Pt 1): E504-E512
1996
ISSN/ISBN: 0002-9513 PMID: 8638699 Document Number: 461206
The role of P-2 purinoceptor agonists in regulatory insulin secretion in Zucker diabetic fatty (ZDF) rats was studied using the isolated perfused pancreas and intracellular Ca-2+ concentration ((Ca-2+)-i) microfluorimetry. The relative potency of different purinoceptor agonists to stimulate the insulin secretory process was consistent with the conclusion that responses in (Ca-2+)-i and insulin secretion are mediated by the P-2y subtype of purinoceptors. Additional studies using specific antagonists of the Ca-2+ signaling pathway indicated that activation of P-2y purinoceptor releases Ca-2+ from intracellular stores and promotes Ca-2+ entry through voltage-independent rather than voltage-dependent Ca-2+ channels on the beta-cell membrane. Perfused pancreas and isolated islets from ZDF rats demonstrated markedly reduced or absent insulin secretion and (Ca-2+)-i responses to glucose and KCl. In contrast, responses to P-2y 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.