Modulation by IBMX, fasting and experimental diabetes of glibenclamide-induced islet hormone release from the perfused rat pancreas

Abstract

The impact of increased c-AMP levels, short-term fasting as well as experimental diabetes on glibenclamide-induced secretion of somatostatin, insulin and glucagon was studied in the isolated perfused rat pancreas. Dose-response curves revealed that 1 microgram/ml of glibenclamide (in the presence of 3.3 mmol/l of glucose) induced maximal stimulation of insulin and near maximal stimulation of somatostatin release, but did not significantly affect glucagon release. A combination of glibenclamide and the phosphodiesterase inhibitor IBMX synergistically and equally increased both B- and D-cell secretion. Fasting the rats for 24 h significantly suppressed the insulin and glucagon responses to glibenclamide while the concomitant somatostatin response was slightly enhanced. Rats injected with alloxan 3 days prior to perfusion were rendered either moderately diabetic or severely ill with ketoacidosis. Their insulin responses were poor or absent, respectively. In the moderately diabetic rats glibenclamide-induced somatostatin release was blunted while it was abolished in the ketotic rats. The results indicate that glibenclamide-induced B- and D-cell secretion are both modulated by c-AMP, that short-term fasting differentially affects B- and D-cell secretion and that D-cell secretion is inhibited in alloxan diabetes of short duration. It is concluded that the balance of effects by glibenclamide on hormones of the endocrine pancreas may depend on the nutritional and metabolic environment.