title: On-target effects of GLP-1 receptor agonists on thyroid C-cells in rats and mice.
abstract: Glucagon-like peptide-1 is an incretin hormone from the gastrointestinal tract, which enhances insulin secretion, slows gastric emptying, and reduces food intake. GLP-1 receptor agonists are being developed for Type 2 diabetes mellitus. GLP-1 is rapidly degraded by serum dipeptidyl peptidase IV, so analogues with a prolonged serum half-life are used clinically. Exenatide was the first GLP-1 agonist approved and is a synthetic version of exendin-4 derived from the Gila monster. Liraglutide was approved for clinical use in 2010. GLP-1 receptor agonists have been shown to increase calcitonin secretion and stimulate C-cell hyperplasia and neoplasia in rats and mice of both sexes. Rat C-cells are more sensitive to the effects of GLP-1 agonists than mice. The effects of GLP-1 agonists on C-cell proliferation or neoplasia have not been documented in nonhuman primates or humans. The proliferative C-cell effects may be rodent-specific. GLP-1 receptors have been demonstrated on normal rodent C-cells, but are either not present or occur in low numbers on C-cells of nonhuman primates and humans. Hyperplasia and neoplasia of C-cells in rodents treated with GLP-1 agonists represent a unique example of an on-target species-specific effect that may not have relevance to humans.
authors.affiliation: The Ohio State University, Department of Veterinary Biosciences, Columbus, Ohio 43210, USA. rosol.1@osu.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rosol
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D000069450:Liraglutide; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D018027:Receptors, Glucagon / Q000819:agonists*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000139:chemically induced; D014688:Venoms / Q000494:pharmacology
chemical_list: C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide