Effects of glibenclamide and metformin (alone or in combination) on insulin release from isolated human pancreatic islets

Isolated human pancreatic islets were prepared by collagenase digestion and density gradient purification, and the effects of glibenclamide (0.5 and 5.0 mu mol/l) and metformin (20 and 200 mu mol/l), alone or in combination, on insulin release were evaluated at varying glucose concentrations. At 3.3 mmol/l glucose level, the addition of 5.0 mu mol/l glibenclamide or 5.0 mu mol/l glibenclamide plus 200 mu mol/l metformin caused a significant increase of insulin release, compared with glucose alone. At 16.7 mmol/l glucose concentration, a significant increase of insulin secretion, compared with glucose alone, was produced by the addition of either 5.0 mu mol/l glibenclamide, 200 mu mol/l metformin, or both 5.0 mu mol/l glibenclamide and 200 mu mol/l metformin. The effect of the combination of the two drugs was significantly higher than that with either drug used alone. Thus, glibenclamide was shown to have an insulinotropic effect on human islets at bath low and high glucose concentrations, and metformin at high glucose concentrations. A possible synergistic effect of glibenclamide and metformin at high glucose concentrations is also suggested.