title: Do adipocytes contain high affinity sulfonylurea receptors.
abstract: Sulfonylureas interact with specific, high affinity receptors on the pancreatic beta-cell to close ATP-sensitive K+ channels, depolarize the cell, activate Ca2+ influx through voltage-dependent Ca2+ channels, and trigger insulin secretion. We tested the hypothesis that sulfonylureas promote glucose uptake into 3T3-L1 cells or isolated rat adipocytes by similar mechanisms. Using 125I-labeled 5-iodo-2-hydroxyglyburide and either equilibrium binding or photoaffinity labeling, a high affinity sulfonylurea receptor was not found on plasma membranes of either the 3T3-L1 cells or rat adipocytes. Furthermore, glyburide did not inhibit 86Rb+ efflux (a marker for ATP-sensitive K+ channel conductance), increase free cytosolic calcium in adipocytes or 3T3-L1 cells, or increase basal or insulin-stimulated glucose uptake into 3T3-L1 cells or rat adipocytes. Parallel studies using a hamster insulin-secreting tumor cell line (HIT cells) easily demonstrated both the receptor and biological effects of glyburide on free cytosolic calcium and insulin secretion. Thus, rat adipocytes and 3T3-L1 cells do not possess the high affinity sulfonylurea receptor or respond to glyburide alone. We conclude that the antidiabetogenic effects of sulfonylureas are not mediated by a direct action of sulfonylureas to increase glucose uptake into adipose tissue and suggest that the major locus for sulfonylurea action is the beta-cell.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: A S
authors.initials: AS
authors.lastname: Rajan
authors.forename: Z T
authors.initials: ZT
authors.lastname: Luo
authors.forename: B B
authors.initials: BB
authors.lastname: Kahn
authors.forename: J P
authors.initials: JP
authors.lastname: Comstock
authors.forename: S W
authors.initials: SW
authors.lastname: Cushman
authors.forename: A E
authors.initials: AE
authors.lastname: Boyd
mesh_terms: D016475:3T3 Cells; D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D005905:Glyburide / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000502:physiology; D009124:Muscle Proteins; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000032:analysis*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000032:analysis*; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D064233:Sulfonylurea Receptors
chemical_list: D018528:ATP-Binding Cassette Transporters; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; C495693:Slc2a4 protein, mouse; C495694:Slc2a4 protein, rat; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; C064021:5-iodo-2-hydroxyglyburide; D000255:Adenosine Triphosphate; D005947:Glucose; D011188:Potassium; D005905:Glyburide; D002118:Calcium