Characterization of sulfonylurea receptors in isolated human pancreatic islets

✍ Scribed by Gino Giannaccini; Roberto Lupi; M. Letizia Trincavelli; Renzo Navalesi; Laura Betti; Piero Marchetti; Antonio Lucacchini; Silvia Del Guerra; Claudia Martini

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 132 KB
• Volume: 71
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19981101)71:2<182::aid-jcb4>3.0.co;2-r

✦ Synopsis

Current information on pancreatic islet sulfonylurea receptors has been obtained with laboratory animal pancreatic ␤ cells or stable ␤-cell lines. In the present study, we evaluated the properties of sulfonylurea receptors of human islets of Langherans, prepared by collagenase digestion and density-gradient purification. The binding characterisitics of labeled glibenclamide to pancreatic islet membrane preparations were analyzed, displacement studies with several oral hypoglycemic agents were performed, and these latter compounds were tested as for their insulinotropic action on intact human islets. [ 3 H]glibenclamide saturable binding was shown to be linear at Յ0.25 mg/ml protein; it was both temperature and time dependent. Scatchard analysis of the equilibrium binding data at 25°C indicated the presence of a single class of saturable, high-affinity binding sites with a K d value of 1.0 Ϯ 0.07 nM and a Bmax value of 657 Ϯ 48 fmol/mg of proteins. The displacement experiments showed the following rank order of potency of the oral hypoglycemic agents we tested: glibenclamide ϭ glimepiride Ͼ tolbutamide Ͼ chlorpropamide : metformin. This binding potency order was parallel with the insulinotropic potency of the evaluated compounds.