title: Effect of GLP1R agonists taspoglutide and liraglutide on primary thyroid C-cells from rodent and man.
abstract: Glucagon-like peptide 1 (GLP1) analogs have been associated with an increased incidence of thyroid C-cell hyperplasia and tumors in rodents. This effect may be due to a GLP1 receptor (GLP1R)-dependent mechanism. As the expression of GLP1R is much lower in primates than in rodents, the described C-cell proliferative lesions may not be relevant to man. Here, we aimed to establish primary thyroid cell cultures of rat and human to evaluate the expression and function of GLP1R in C-cells. In our experiments, GLP1R expression was observed in primary rat C-cells (in situ hybridization) but was not detected in primary human C-cells (mRNA and protein levels). The functional response of the cultures to the stimulation with GLP1R agonists is an indirect measure of the presence of functional receptor. Liraglutide and taspoglutide elicited a modest increase in calcitonin release and in calcitonin expression in rat primary thyroid cultures. Contrarily, no functional response to GLP1R agonists was observed in human thyroid cultures, despite the presence of few calcitonin-positive C-cells. Thus, the lack of functional response of the human cultures adds to the weight of evidence indicating that healthy human C-cells have very low levels or completely lack GLP1R. In summary, our results support the hypothesis that the GLP1R agonist-induced C-cell responses in rodents may not be relevant to primates. In addition, the established cell culture method represents a useful tool to study the physiological and/or pathological roles of GLP1 and GLP1R agonists on normal, non-transformed primary C-cells from rats and man.
authors: F. Hoffmann-La Roche Ltd., Non Clinical Safety, Grenzacherstrasse 124, 4070 Basel, Switzerland. franziska.boess@roche.com
authors: Franziska
authors: F
authors: Boess
authors: Cristina
authors: C
authors: Bertinetti-Lapatki
authors: Sannah
authors: S
authors: Zoffmann
authors: Catherine
authors: C
authors: George
authors: Thomas
authors: T
authors: Pfister
authors: Adrian
authors: A
authors: Roth
authors: Serene M L
authors: SM
authors: Lee
authors: Wolfgang E
authors: WE
authors: Thasler
authors: Thomas
authors: T
authors: Singer
authors: Laura
authors: L
authors: Suter
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000378:metabolism; D002478:Cells, Cultured; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D000069450:Liraglutide; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D018027:Receptors, Glucagon / Q000819:agonists*; D013961:Thyroid Gland / Q000166:cytology*; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014284:Triiodothyronine; C541736:taspoglutide; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D002116:Calcitonin