Evidence of Functional Gastric Inhibitory Polypeptide (GIP) Receptors in Human Insulinoma: Binding of Synthetic Human GIP 1-31 and Activation of Adenylate Cyclase Free

Specific gastric inhibitory polypeptide (GIP) receptors were characterized in human benign insulinoma plasma membranes employing [mono-[^125l]iodo-Tyr10]- GIP (¹²⁵I-GIP) as the radioligand. GIP 1-42 inhibited ¹²⁵I-GIP binding with an IC₅₀ value of ⁻⁹ M. Scatchard analysis showed two classes of binding sites: a highaffinity site (K_d = 2.23 × ⁻⁹ M; B^max = 24 fmol/mg protein) and a low-affinity site (K_d = 8.39 × 10⁻⁹ M; B^max = 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 β-cell function in humans through a purely endocrine pathway.