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Characterization of sulfonylurea receptors in isolated human pancreatic islets
Author(s) -
Giannaccini Gino,
Lupi Roberto,
Trincavelli M. Letizia,
Navalesi Renzo,
Betti Laura,
Marchetti Piero,
Lucacchini Antonio,
Guerra Silvia Del,
Martini Claudia
Publication year - 1998
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19981101)71:2<182::aid-jcb4>3.0.co;2-r
Subject(s) - glibenclamide , chlorpropamide , tolbutamide , sulfonylurea , receptor , endocrinology , medicine , sulfonylurea receptor , glipizide , chemistry , islet , pancreatic islets , potency , glimepiride , insulin , in vitro , biology , biochemistry , metformin , diabetes mellitus
Current information on pancreatic islet sulfonylurea receptors has been obtained with laboratory animal pancreatic β cells or stable β‐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 ≤0.25 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 ± 0.07 nM and a Bmax value of 657 ± 48 fmol/mg of proteins. The displacement experiments showed the following rank order of potency of the oral hypoglycemic agents we tested: glibenclamide = glimepiride > tolbutamide > chlorpropamide ≫ metformin. This binding potency order was parallel with the insulinotropic potency of the evaluated compounds. J. Cell. Biochem. 71:182–188, 1998. © 1998 Wiley‐Liss, Inc.