The pancreatic β-cell recognition of insulin secretagogues

Summary The study was aimed at testing the hypothesis that sulfonylureas do not readily penetrate the pancreatic-cells but more probably stimulate insulin release by a direct action on the-cell plasma membrane. Uptake of radioactively labelled tolbutamide and glibenclamide by microdissected pancreatic islets of obesehyperglycemic mice was compared with the uptake of 3-O-methyl-D-glucose, to which the-cells are permeable. In contrast to tolbutamide, glibenclamide was taken up in amounts exceeding the 3-O-methyl-D-glucose space of islets incubated in the absence of serum albumin. Uptake of the sulfonylureas was easily reversible. It was depressed by serum albumin, whereas glucose, leucine or diazoxide had no effects. Antimycin A,p-chloromercuriphenylsulfonic acid and chlorpromazine, all of which increase the uptake of extracellular space markers, strongly stimulated the islet uptake of tolbutamide and glibenclamide but had no effect on the uptake of glibenclamide by subcellular particles of homogenized islets. The results suggest that sulfonylureas bind reversibly to islet tissue but are normally restricted to the outside of the-cells.