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  • Title: Preservation of insulin secretory responses to P2 purinoceptor agonists in Zucker diabetic fatty rats.
    Author: Tang J, Pugh W, Polonsky KS, Zhang H.
    Journal: Am J Physiol; 1996 Mar; 270(3 Pt 1):E504-12. PubMed ID: 8638699.
    Abstract:
    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.
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