title: Incretin receptors in non-neoplastic and neoplastic thyroid C cells in rodents and humans: relevance for incretin-based diabetes therapy.
abstract: 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.
authors: Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland.
authors: Beatrice
authors: B
authors: Waser
authors: Karin
authors: K
authors: Beetschen
authors: Natalia S
authors: NS
authors: Pellegata
authors: Jean Claude
authors: JC
authors: Reubi
mesh_terms: D000818:Animals; D018278:Carcinoma, Neuroendocrine; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000628:therapy; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D018027:Receptors, Glucagon / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; C041086:gastric inhibitory polypeptide receptor