title: Preservation of insulin secretory responses to P2 purinoceptor agonists in Zucker diabetic fatty rats.
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.
authors.affiliation: Department of Medicine, The University of Chicago, Illinois 06037, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tang
authors.forename: W
authors.initials: W
authors.lastname: Pugh
authors.forename: K S
authors.initials: KS
authors.lastname: Polonsky
authors.forename: H
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009765:Obesity; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D012016:Reference Values; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001786:Blood Glucose; C092578:FPL 66301; D007328:Insulin; D058910:Purinergic P2 Receptor Agonists; D013873:Thionucleotides; C030812:adenosine 5'-O-(2-thiodiphosphate); D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D000241:Adenosine; D002118:Calcium