Evidence for a functional role of the cholecystokinin-B/gastrin receptor in the human fetal and adult pancreas
| Autor: | Pascal Clerc, Christine Moriscot, H. Corominola, Chantal Escrieut, Corinne Saillan-Barreau, Daniel Fourmy, O Guy-Crotte, Marlène Dufresne, R Gomis, Nicole Vaysse, D. Sanchez, N Tarasova |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
endocrine system medicine.medical_specialty Endocrinology Diabetes and Metabolism Receptor expression Biology Glucagon Internal medicine Gastrins Internal Medicine medicine Humans RNA Messenger Cloning Molecular Pancreas Cells Cultured Glucagon-like peptide 1 receptor Cholecystokinin Gastrin geography geography.geographical_feature_category digestive oral and skin physiology Glucagon secretion Islet Receptor Cholecystokinin B Endocrinology Gene Expression Regulation Gastrointestinal hormone Receptors Cholecystokinin hormones hormone substitutes and hormone antagonists |
| Zdroj: | Diabetes. 48:2015-2021 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.48.10.2015 |
| Popis: | Gastrin (G) and cholecystokinin (CCK) are gastrointestinal neuropeptides that are released into circulation during a meal. G is also transiently expressed during embryogenic and early ontogenic development of the pancreas and is believed to act on islet-cell development. Both peptides act on pancreatic endocrine function; however, the effects are dependent on the species and on cellular and molecular underlying mechanisms that remain poorly characterized. Since CCK-B/G subtype receptor is predominant over the CCK-A subtype in the human pancreas, we hypothesized that it could be expressed by islet cells. Here we present reverse transcription-polymerase chain reaction and immunohistochemistry data demonstrating that the CCK-B/G receptor is expressed in islet cells and that islet glucagon-producing cells are the major site of CCK-B/G receptor expression in adult and fetal pancreas. Moreover, G immunoreactivity was detected in the fetal human pancreas at embryogenic week 22. G- and CCK-stimulated glucagon are released from purified human islets. Concentration of CCK and G eliciting a half-maximal level of glucagon secretion were 13 +/- 6 and 8 +/- 5 pmol/l, respectively. Maximal glucagon secretion was achieved in the presence of 30 pmol/l peptides and was similar to that obtained in the presence of 10 mmol/l L-arginine (1.6 pmol x ml(-1) x 90 min(-1)). The nonpeptide antagonist of the CCK-B/G receptor, RPR-101048, fully inhibited CCK- and G-stimulated glucagon secretion at 100 nmol/l concentration. These data are consistent with the view that the CCK-B/G receptor is involved in glucose homeostasis in adult humans and mediates the autocrine effects of G on islet differentiation and growth in the fetal pancreas. |
| Databáze: | OpenAIRE |
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