Prior glucose deprivation increases the first phase of glucose-induced insulin response: possible involvement of endogenous ATP and (or) ADP.

A possible implication of endogenously released ATP and (or) ADP in insulin response to glucose stimulation was investigated in the isolated rat pancreas. The first phase of insulin response to the same glucose concentration (8.3 mM) was much higher in pancreas previously perfused in the absence of glucose than in pancreas previously perfused with 4.2 mM glucose. A P2 purinoceptor antagonist, 2,2'-pyridylisatogen tosylate, strongly reduced the higher first phase resulting from glucose deprivation; similarly, it reduced exogenous ATP-potentiated insulin response to a glucose increase from 4.2 to 8.3 mM. In contrast, 2,2'-pyridylisatogen tosylate did not modify the first phase of insulin response to 8.3 or 12.5 mM glucose in pancreas previously perfused with 4.2 mM glucose. Our results suggest that endogenous ATP and (or) ADP released in pancreatic islets in the absence of glucose could activate P2 purinoceptors and increase the magnitude of the first phase of insulin response to a glucose stimulation.