Factors affecting the uptake of glibenclamide in microdissected pancreatic islets rich in beta-cells.

Abstract

The uptake of radioactively labelled glibenclamide was studied in microdissected pancreatic islets of obese-hyperglycemic mice. The steady-state concentration reached was linearly related to the medium concentration of glibenclamide. This is in contrast to the short-term uptake, for which there was evidence for saturation. The amounts of glibenclamide incorporated increased by more than 100 % when the plasma membranes were made permeable to sucrose by reducing the osmolality of the incubation medium. No binding of glibenclamide in excess of sucrose could be detected after increasing the albumin concentration to 10 mg/ml. The steady-state concentrations reached were approximately the same in the presence of different monovalent cations. The observation of a reduced uptake of glibenclamide in the presence of cysteine raises the question whether sulfonylureas stimulate insulin release by reacting with sulf-hydryl groups in the /3-cell membrane.