Should we still be concerned about the potential side effects of glucagon-like peptide-1 receptor agonists on thyroid C
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REVIEW
Should we still be concerned about the potential side effects of glucagon-like peptide-1 receptor agonists on thyroid C cells? Yang Cao • Xiao-Min Liu
Received: 22 April 2014 / Accepted: 29 June 2014 Ó Springer Science+Business Media New York 2014
Abstract In recent years, numerous novel anti-diabetic drugs have emerged. Among them, glucagon-like peptide-1 receptor (GLP-1R) agonists developed on the basis of the incretin theory are the most popular and surprising. Thus far, the clinical and experimental efficiency and safety data seem to be good. However, questions about the side effects of GLP-1R agonists, especially on thyroid C cells, still remain. In vivo and in vitro rodent experiments have shown the potential risks of GLP-1R agonists on thyroid C cells. However, the effects of GLP-1R agonists in humans, which have only been studied in experiments using untreated thyroid tissues or C-cell lines, are questionable and differ from that in rodents. C-cell abnormalities are not only dependent on GLP-1R, as many other factors also influence the structure and function of thyroid C cells. Furthermore, there is not enough information from patients with diabetes or tissue samples from subjects treated with GLP-1R agonists and related drugs—especially data obtained during the prandial period or from a long-term study. Therefore, it is important to focus on the possible side effects of GLP-1R agonists on thyroid C cells. Keywords Glucagon like peptide-1 receptor (GLP-1R) agonists Thyroid C cells Proton pump inhibitor (PPI) Gastrin
Abbreviations GLP-1 GLP-1R GLP-1Rs PPI Ct PTH MTC MEN2 PTC CEA RET GERD Px DPP-4i NOD CCK-BR/gastrin receptors H2RB PA AN
Glucagon-like peptide-1 Glucagon-like peptide-1 receptor Glucagon-like peptide-1 receptors Proton pump inhibitor Calcitonin Parathyroid hormone Medullary thyroid carcinoma Multiple endocrine neoplasia 2 Papillary thyroid carcinoma Carcinoembryonic antigen Rearranged during transfection Gastroesophageal reflux disease Partial pancreatectomy Dipeptidyl-peptidase IV inhibitor Non-obese diabetic Cholecystokinin-B receptors Histamine2 receptor blocker Pernicious anaemia Autonomic neuropathy
Introduction
Y. Cao X.-M. Liu (&) Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, No. 24 Youzheng Street, Harbin 150001, Heilongjiang Province, China e-mail: [email protected]
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is secreted from intestinal endocrine L cells located mainly in the distal ileum and colon [1]. GLP-1 receptor (GLP-1R) agonists developed based on the incretin theory have many physiological effects, particularly on the regulation of glucose homeostasis, such as stimulation of
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Endocrine
glucose-dependent insulin secretion [2], promotion of bcell proliferation [3], suppression of glucagon release [4], reduction of energy intake [5, 6], and delay of gastric emptying [7, 8]. But, these drugs also have their own shortings. In rodents, GLP-1R agonists can induce calcitonin (Ct) secretion, C-cell
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