title: Evidence of functional gastric inhibitory polypeptide (GIP) receptors in human insulinoma. Binding of synthetic human GIP 1-31 and activation of adenylate cyclase.
abstract: Specific gastric inhibitory polypeptide (GIP) receptors were characterized in human benign insulinoma plasma membranes employing [mono-[125I]iodo-Tyr10]-GIP (125I-GIP) as the radioligand. GIP 1-42 inhibited 125I-GIP binding with an IC50 value of 10(-9) M. Scatchard analysis showed two classes of binding sites: a high-affinity site (Kd = 2.23 x 10(-10) M; Bmax = 24 fmol/mg protein) and a low-affinity site (Kd = 8.39 x 10(-9) M; Bmax = 118 fmol/mg protein). A synthetic replicate of human GIP 1-31 inhibited 125I-GIP binding with an IC50 value of 10(-8) M. The GIP binding sites of human insulinoma were coupled to adenylate cyclase stimulation. GIP 1-31 regulated the adenylate cyclase activity to the same extent as GIP 1-42. The concentrations of GIP required for maximal activity ranged from 10(-9) to 10(-8) M for either GIP 1-42 or GIP 1-31. The existence of functional GIP receptors in human insulinoma substantiates our recent reports demonstrating the presence of GIP binding sites in transplantable hamster insulinoma and indicates that GIP could exert a direct control of the beta-cell function in humans through a purely endocrine pathway.
authors.affiliation: Fondation de Recherche en Hormonologie, Fresnes, France.
authors.forename: M
authors.initials: M
authors.lastname: Maletti
authors.forename: J J
authors.initials: JJ
authors.lastname: Altman
authors.forename: D H
authors.initials: DH
authors.lastname: Hoa
authors.forename: M
authors.initials: M
authors.lastname: Carlquist
authors.forename: G
authors.initials: G
authors.lastname: Rosselin
mesh_terms: D007516:Adenoma, Islet Cell / Q000378:metabolism*; D000328:Adult; D002462:Cell Membrane / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D006801:Humans; D007340:Insulinoma / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*
chemical_list: D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor