adp-beta-s and Obesity

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.

Topics: Adenosine; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Analysis of Variance; Animals; Blood Glucose; Body Weight; Calcium; Diabetes Mellitus; Diabetes Mellitus, Type 2; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Kinetics; Male; Obesity; Perfusion; Potassium Chloride; Purinergic P2 Receptor Agonists; Rats; Rats, Wistar; Rats, Zucker; Reference Values; Thionucleotides; Time Factors