The in vivo interaction between gliclazide and glibenclamide and insulin on glucose disposal in the rat

Many reports suggest that extrapancreatic actions contribute to the antidia betic effect of sulphonylurea drugs (SUs). In this work, the ability of two SUs, namely, gliclazide and glibenclamide, to augment insulin action was s tudied in vivo. Both drugs elevated the plasma concentration of immunoreact ive insulin (IRI) and lowered the plasma concentrations of glucose and non- esterified fatty acids (NEFA) in normal intact rats. These changes were not reproduced in alloxan-diabetic or eviscerated rats. The actions of insulin on plasma glucose and NEFA were not augmented by gliclazide in alloxan-dia betic rats. Neither gliclazide nor glibenclamide (given acutely and for 30 days) augmented the actions of exogenously administered insulin in reducing plasma glucose or NEFA concentrations in intact or eviscerated animals. It was concluded that these SUs do not produce their acute or chronic effects on blood glucose by augmenting the actions of insulin. (C) 1999 Academic P ress.