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- Title
P2Y Purinergic Potentiation of Glucose-Induced InsulinSecretion and Pancreatic β-Cell Metabolism.
- Authors
Farret, A.; Vignaud, M.; Dietz, S.; Vignon, J.; Petit, P.; Gross, R.
- Abstract
Purine nucleotides and their analogs increase insulin secretion through activation of pancreatic β-cell P2Y receptors. The present study aimed at determining the role of glucose metabolism in the response to P2Y agonists and whether ATP-activated K[sup+] channels (K[subATP] channels) are involved in this response. The experiments were performed in the rat isolated pancreas, perfused with a Krebs-bicarbonate buffer supplemented with 2 g/l bovine serum albumin under dynamic glucose conditions from 5 mmol/l baseline to 11 retool/l. ADPβS (0.5 µmol/l) was selected as a stable and selective P2Y agonist. This compound, ineffective on the 5 mmol/l glucose background, induced a significant threefold increase in insulin release triggered by the glucose challenge. The effect of ADPβS was markedly reduced (P < 0.001) in the presence of an inhibitor of glucose metabolism. In addition to glucose, the ADP analog also amplified the β-cell insulin response to 15 mmol/l methyl pyruvate (P < 0.05), but it was ineffective on the insulin response to 2.5 mmol/l methyl succinate. A nonmetabolic stimulus was applied using tolbutamide (185 µmol/l). Insulin secretion induced by the K[subATP] channel blocker was strongly reinforced by ADPβS (P < 0.001), which prompted us to check a possible interplay of K[subATP] channels in the effect of ADPβS. In the presence of diazoxide 250 µmol/l and 21 mmol/l KCl, ADPβS still amplified the second phase of glucose-induced insulin secretion (P < 0.001). We conclude that P2Y receptor activation is able to promote insulin secretion through a mechanism, involving β-cell metabolism and a rise in intracellular calcium; this effect does not result from a direct inhibitory effect on K[subATP] channels. Diabetes 53 (Suppl. 3):S63-S66, 2004
- Subjects
PURINE nucleotides; INSULIN; PANCREATIC beta cells; ADENOSINE triphosphate; SERUM albumin; ADENOSINE diphosphate; CELL metabolism; TOLBUTAMIDE
- Publication
Diabetes, 2004, Vol 53, pS63
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.53.suppl_3.S63