title: Functional GIP receptors in a hamster pancreatic beta cell line, In 111: specific binding and biological effects.
abstract: Specific binding sites for GIP have been characterized in a insulin-secreting pancreatic tumor cell line, In 111. The specific binding of 125I-GIP is time, temperature and cells concentration dependent. Under steady state conditions (2 hours at 13 degrees C) specific binding of 125I-GIP (0.3 nM) is competitively inhibited by increasing concentrations of native GIP from 10(-10) to 10(-6) M. Scatchard analysis reveals the presence of two types of sites: a high affinity (KD = 7 nM)/low capacity (3000 sites/cell) site and a low affinity (KD = 800 nM)/high capacity (150,000 sites/cell) site. No other peptide structurally related or not to GIP, interacts with GIP receptors. GIP (10(-10) to 10(-6) M) is able to potently stimulate insulin release in In 111 cells. At 37 degrees C, the stimulation is rapid and reaches a maximum from 30 minutes of incubation. Half-maximal stimulation is elicited by 10 nM GIP and maximal effect reaches 3 times the basal level of insulin release. Concomitantly, GIP (10(-10) - 10(-6) M) increases the basal cyclic AMP level in the cells. Half-maximal stimulation is observed in the presence of 30 nM GIP, maximal stimulation induced by 10(-6) M peptide increases up to 4 times the basal cyclic AMP production. In conclusion, our data provide the first description of a functional GIP receptor in an insulin-secreting pancreatic beta cell.
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism* / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone; D013997:Time Factors
chemical_list: D005768:Gastrointestinal Hormones; D007328:Insulin; D011956:Receptors, Cell Surface; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor; D000242:Cyclic AMP