Incretin receptors in non-neoplastic and neoplastic thyroid C cells in rodents and humans: relevance for incretin-based diabetes therapy

Neuroendocrinology. 2011;94(4):291-301. doi: 10.1159/000330447. Epub 2011 Sep 2.


While incretins are of great interest for the therapy of diabetes 2, the focus has recently been brought to the thyroid, since rodents treated with glucagon-like peptide-1 (GLP-1) analogs were found to occasionally develop medullary thyroid carcinomas. Incretin receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) were therefore measured in various rodent and human thyroid conditions. In vitro GLP-1 and GIP receptor autoradiography were performed in normal thyroids, C-cell hyperplasia and medullary thyroid carcinomas in rodents. Receptor incidence and density were assessed and compared with the receptor expression in human thyroids, medullary thyroid carcinomas, and TT cells. GLP-1 receptors are expressed in C cells of normal rat and mice thyroids. Their density is markedly increased in rat C-cell hyperplasia and medullary thyroid carcinomas, where their incidence amounts to 100%. GIP receptors are neither detected in normal rodent thyroids nor in C-cell hyperplasia, but are present in all rat medullary thyroid carcinomas. No GLP-1 or GIP receptors are detected in normal human thyroids. Whereas only 27% of all human medullary thyroid carcinomas express GLP-1 receptors, up to 89% express GIP receptors in a high density. TT cells lack GLP-1 receptors but express GIP receptors. GLP-1 receptors are frequently expressed in non-neoplastic and neoplastic C cells in rodents while they are rarely detected in human C-cell neoplasia, suggesting species differences. Conversely, GIP receptors appear to be massively overexpressed in neoplastic C cells in both species. The presence of incretin receptors in thyroid C cell lesions suggests that this organ should be monitored before and during incretin-based therapy of diabetes.

MeSH terms

  • Animals
  • Carcinoma, Neuroendocrine
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / therapy
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Incretins / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptors, Gastrointestinal Hormone / metabolism*
  • Receptors, Glucagon / metabolism*
  • Thyroid Gland / metabolism*
  • Thyroid Neoplasms / metabolism*
  • Tumor Cells, Cultured


  • GLP1R protein, human
  • Glp1r protein, mouse
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Incretins
  • Receptors, Gastrointestinal Hormone
  • Receptors, Glucagon
  • gastric inhibitory polypeptide receptor

Supplementary concepts

  • Thyroid cancer, medullary