Preservation of insulin secretory responses to P2 purinoceptor agonists in Zucker diabetic fatty rats.
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.
Tang
J
J
Department of Medicine, The University of Chicago, Illinois 06037, USA.
Pugh
W
W
Polonsky
K S
KS
Zhang
H
H
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
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