Changes in glucose-stimulated insulin secretion after long-term treatment of C57BL mice with glibenclamide

An insulin response to increased glucose concentrations could not be found in vivo and in vitro after long-term treatment of C57BL/KsJ and C57BL/6J mice with Glibenclamide. This missing stimulation of insulin secretion was not the result of an exhaustion of the islets or a disturbed (pro)insulin biosynthesis as demonstrated by measurements of insulin content of the islets and by in vitro (pro)insulin biosynthesis experiments. In the presence of glucose (15 mmol/l) theophylline increased the insulin secretion of isolated islets of Glibenclamide-treated mice to values similar to control islets. The insulin response to an i.p. glucose loading was found to be normal in comparison with control mice 1-2 weeks after the Glibenclamide treatment had been finished.