Studies on the Dynamics and Mechanism of Glibenclamide-Induced Insulin Secretion

Abstract

Sustained, 60-minute perfusion of glibenclamide (0.5, 1.5 and 10 µg/ml) elicits a one-phase insulin release profile, formed by a rapid secretion peak followed by a second peak with lower insulin levels than the former. Basal insulin secretion values are observed during the period comprised between 13 and 60 minutes of perfusion. Concurrent stimulation with glucose (100, 150, 200 and 300 mg%) plus glibenclamide (1 µg(ml) causes a marked rise in both phases of insulin secretion. The addition of glibenclamide does not modify the biphasic secretion pattern caused by maximal glucose concentration (400 mg%). The maximal values of both phases of secretion in the dose-response curve elicited by different glucose concentrations shift to the left when glibenclamide is added to the perfusate. The increase in insulin secretion caused by glibenclamide is not inhibited by puromycin.

Both theophylline and phentolamine modify and increase the glibenclamide-induced insulin release pattern. Propranolol and imidazole inhibit glibenclamide-induced insulin release.

Our results suggest that: 1. Glibenclamide increases beta cell sensitivity to glucose stimulation.
2. Glibenclamide and glucose induce secretion of insulin originating in the same compartment.
3. Modification of alpha and beta adrenergic receptors may modify glibenclamide-induced insulin secretion.
4. 3'5' adenosine monophosphate levels modulate the beta cell response to glibenclamide.

Key words

Insulin Secretion - Glibenclamide - Adrenergic Receptors - Sulfonylurea-Glucose Interaction

1 Present address: Fundación Laboratorios de Investigaciones Pediátricas, Hospital de Pediatría "Pedro de Elizalde", Buenos Aires, Argentina.

2 Member of the Carrera del Investigador Científico, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.