Signal transduction of the GLP‐1‐receptor cloned from a human insulinoma

FEBS Letters

Göke, Rüdiger¹  Lankat-Buttgereit, Brigitte¹  Göke, Burkhard¹  van Eyll, Brigitte¹  Bode, Hans P.² 

[1] Clinical Research Unit for Gastrointestinal Endocrinology Philipps University of Marburg, 35033 Marburg, Germany;Department of Pharmacology, Philipps University of Marburg, 35033 Marburg, Germany

关键词: Human insulinoma;    GLP-1 receptor;    COS-7 cell;    CHL cell;    Calcium;    cAMP;   

DOI  :  10.1016/0014-5793(94)00553-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

GLP-1 (glucagon-like peptide 1 (7–36) amide) plays an important role in the regulation of insulin secretion and proinsulin gene expression of pancreatic β-cells. Patients with insulinoma tumors show uncontrolled insulin hypersecretion. This study demonstrates the molecular cloning of a cDNA for the GLP-1 receptor from a human insulinoma employing a λ-gt 11 cDNA library. The cloned cDNA encoded a seven transmembrane domain protein of 463 amino acids which showed high homology to the GLP-1 receptor in normal human pancreas. Four amino acid exchanges were found in comparison to a receptor sequence obtained from regular pancreatic islets. When transfected transiently into COS-7 or stably into fibroblast CHL cells a high affinity receptor was expressed which coupled to the adenylate cyclase with normal basal cAMP and increasing intracellular cAMP levels under GLP-1 stimulation. The receptor accepted GLP-1 and the non-mammalian agonist exendin-4 as high affinity ligands. In transfected COS-7 cells, GLP-1 did not influence intracellular calcium, whereas in the stably transfected fibroblasts GLP-1 transiently increased intracellular calcium to a small extent. The understanding of GLP-1 receptor regulation and signal transduction will aid in the discovery of compounds that act as agonists of the GLP-1 receptor for potential use in the treatment of diabetes and will facilitate the understanding of its expression under normal and pathophysiological conditions.

【 授权许可】

Unknown