Glibenclamide is exceptional among hypoglycaemic sulphonylureas in accumulating progressively in β-cell-rich pancreatic islets

Abstract

Six hypoglycemic sulfonylurea compounds [used in diabetes treatment] were compared with regard to their ability to bind to .beta.-cell-rich pancreatic islets microdissected from ob/ob-mice. Gibenclamide 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''-disulfonic 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.