Glibenclamide is exceptional among hypoglycaemic sulphonylureas in accumulating progressively in beta-cell-rich...

Six hypoglycaemic sulphonylurea compounds were compared with regard to their ability to bind to beta-cell-rich pancreatic islets microdissected from ob/ob-mice. Glibenclamide differed from carbutamide, tolbutamide, chlorpropamide, glibornuride and glipizide in not being rapidly bound to an equilibrium, but accumulating progressively in amounts far exceeding the water space. An inhibitor of the anion channels in the beta-cell membrane, 4-acetamido-4'-isothiocyanate-stilbene-2,2'-disulphonic acid (SITS), suppressed the islet uptake of glibenclamide and to some extent also that of carbutamide and glibornuride. The unusual uptake characteristics of glibenclamide had their counterpart in a retardation of its maximal action in promoting the entry of Ca2+ into the beta-cells.