CHARACTERIZATION OF SULFONYLUREA RECEPTORS IN ISOLATED HUMAN PANCREATIC-ISLETS

Current information on pancreatic islet sulfonylurea receptors has bee n obtained with laboratory animal pancreatic beta cells or stable beta -cell lines. In the present study, we evaluated the properties of sulf onylurea receptors of human islets of Langherans, prepared by collagen ase digestion and density-gradient purification. The binding character isitics of labeled glibenclamide to pancreatic islet membrane preparat ions were analyzed, displacement studies with several oral hypoglycemi c agents were performed, and these latter compounds were tested as for their insulinotropic action on intact human islets. [H-3]glibenclamid e saturable binding was shown to be linear at less than or equal to 0. 25 mg/ml protein; it was both temperature and time dependent. Scatchar d analysis of the equilibrium binding data at 25 degrees C indicated t he presence of a single class of saturable, high-affinity binding site s with a K-d value of 1.0 +/- 0.07 nM and a Bmax value of 657 +/- 48 f mol/mg of proteins. The displacement experiments showed the following rank order of potency of the oral hypoglycemic agents we tested. glibe nclamide = glimepiride > tolbutamide > chlorpropamide >> metformin. Th is binding potency order was parallel with the insulinotropic potency of the evaluated compounds. I. Cell. Biochem. 77:182-188, 1998. (C) 19 98 Wiley-Liss, Inc.