Glucose-dependent insulinotropic polypeptide receptors in most gastroenteropancreatic and bronchial neuroendocrine tumors

J Clin Endocrinol Metab. 2012 Feb;97(2):482-8. doi: 10.1210/jc.2011-2454. Epub 2011 Nov 23.


Context: Gastrointestinal peptide hormone receptors overexpressed in neuroendocrine tumors (NET), such as somatostatin or glucagon-like peptide-1 (GLP-1) receptors, are used for in vivo tumor targeting. Unfortunately, not all NET express these receptors sufficiently.

Objective: Our aim was to evaluate in vitro the expression of another incretin receptor, glucose-dependent insulinotropic polypeptide (GIP) receptor, in human tumors and compare it with that in adjacent nonneoplastic tissues and also with somatostatin and GLP-1 receptor expression.

Methods: GIP receptor protein expression was qualitatively and quantitatively investigated in 260 human tumors and in nonneoplastic human tissues with receptor autoradiography using [(125)I]GIP(1-30). Pharmacological competition experiments and mRNA analysis were performed to provide proof of specificity. Somatostatin receptor and GLP-1 receptor autoradiography were performed in adjacent sections.

Results: GIP receptors are expressed in the majority of pancreatic, ileal, and bronchial NET. Importantly, most of the somatostatin receptor-negative NET and GLP-1 receptor-negative malignant insulinomas are GIP receptor positive. Conversely, the epithelial and stromal gastrointestinal tumors, including gastric, colonic, and hepatocellular carcinomas, cholangiocarcinomas, and gastrointestinal stromal tumors as well as lung adenocarcinomas are usually GIP receptor negative, except for 26% of pancreatic adenocarcinomas. Pancreatic islets, but not acini, are GIP receptor positive. The rank order of potencies for receptor binding and mRNA analysis by PCR reveal specific GIP receptors.

Conclusions: The numerous GIP receptors in gastroenteropancreatic and bronchial NET represent novel universal molecular targets for clinical applications, in particular for in vivo scintigraphy and targeted radiotherapy. These results may also be the basis for multiple targeting, with concomitant use of GIP, somatostatin, and GLP-1 analogs as radiotracers.

MeSH terms

  • Bronchial Neoplasms / genetics*
  • Bronchial Neoplasms / metabolism
  • Bronchial Neoplasms / pathology
  • Gastric Inhibitory Polypeptide / pharmacokinetics
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / metabolism
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / pathology
  • Gene Expression Regulation, Neoplastic
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Iodine Radioisotopes / pharmacokinetics
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology
  • Osmolar Concentration
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Peptide Fragments / pharmacokinetics
  • Receptors, Gastrointestinal Hormone / agonists
  • Receptors, Gastrointestinal Hormone / genetics*
  • Receptors, Gastrointestinal Hormone / metabolism
  • Receptors, Glucagon / genetics
  • Receptors, Glucagon / metabolism
  • Tissue Distribution


  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Iodine Radioisotopes
  • Peptide Fragments
  • Receptors, Gastrointestinal Hormone
  • Receptors, Glucagon
  • gastric inhibitory polypeptide (1-30)
  • Gastric Inhibitory Polypeptide
  • gastric inhibitory polypeptide receptor