Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma

FEBS Lett. 1995 Oct 2;373(1):23-9. doi: 10.1016/0014-5793(95)01006-z.


Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells. This study demonstrates the molecular cloning of a cDNA for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. The cloned cDNA encoded a seven transmembrane domain protein of 466 amino acids which showed high homology (41%) to the human glucagon-like peptide 1 (GLP-1) receptor. Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively. When transfected 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 stimulation with human GIP-1-42 (EC50 = 1.29 x 10(-13) M). The receptor accepted only human GIP 1-42 (Kd = 1.93 +/- 0.2 x 10(-8) M) and porcine truncated GIP 1-30 (Kd = 1.13 +/- 0.1 x 10(-8) M) as high affinity ligands. At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP-binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl cyclase activating peptide were without effect. In transfected CHL cells, GIP-1-42 did not increase intracellular calcium. Northern analysis revealed one transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. The exact understanding of GIP receptor regulation and signal transduction will aid in the understanding of the incretin hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding, Competitive
  • Clone Cells
  • Cricetinae
  • Gastric Inhibitory Polypeptide / metabolism
  • Gene Library
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Insulinoma / metabolism*
  • Kinetics
  • Molecular Sequence Data
  • Pancreatic Neoplasms / metabolism*
  • Peptide Fragments / metabolism
  • Protein Precursors / metabolism
  • Rats
  • Receptors, Gastrointestinal Hormone / biosynthesis*
  • Receptors, Gastrointestinal Hormone / chemistry
  • Receptors, Gastrointestinal Hormone / physiology*
  • Receptors, Glucagon / chemistry
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Substrate Specificity
  • Swine
  • Transfection
  • Tumor Cells, Cultured


  • GLP1R protein, human
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Protein Precursors
  • Receptors, Gastrointestinal Hormone
  • Receptors, Glucagon
  • Recombinant Proteins
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon
  • gastric inhibitory polypeptide receptor

Associated data

  • GENBANK/S79852