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Waser, B.* ; Beetschen, K.* ; Pellegata, N.S. ; Reubi, J.C.*

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

Neuroendocrinology 94, 291-301 (2011)

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Open Access Green as soon as Postprint is submitted to ZB.

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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 vitroGLP-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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Diabetes therapy; GIP receptors; GLP-1 receptors; Incretin receptors; Medullary thyroid carcinomas; Thyroid C cells

ISSN (print) / ISBN 0028-3835

e-ISSN 1423-0194

Journal Neuroendocrinology

Quellenangaben Volume: 94, Issue: 4, Pages: 291-301

Publisher Karger

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Pathology (PATH)