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Effects of insulin analogs and glucagon-like peptide-1 receptor agonists on proliferation and cellular energy metabolism in papillary thyroid cancer

Authors He L, Zhang S, Zhang X, Liu R, Guan H, Zhang H

Received 2 September 2017

Accepted for publication 1 November 2017

Published 24 November 2017 Volume 2017:10 Pages 5621—5631

DOI https://doi.org/10.2147/OTT.S150701

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai


Liang He,1,* Siliang Zhang,2,* Xiaowen Zhang,3 Rui Liu,2 Haixia Guan,2 Hao Zhang1

1Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, 2Department of Endocrinology and Metabolism, The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, 3Department of Endocrinology and Metabolism, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, People’s Republic of China

*These authors contributed equally to this work

Purpose: This study was aimed to investigate the expressions of the insulin receptor (IR), insulin-like growth factor receptor (IGF-1R), and glucagon-like peptide-1 receptor (GLP-1R) in normal thyroid tissue, papillary thyroid cancer (PTC) tissues, and PTC cells, and to examine the possible role of insulin analogs and GLP-1R agonists in cell proliferation and energy metabolism in PTC cells.
Methods: The expressions of IR, IGF-1R, and GLP-1R in PTC tissues and PTC cell lines were detected by immunohistochemistry and western blotting, respectively. Cell proliferation was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Levels of members of the phosphoinositol-3 kinase/AKT serine/threonine kinase (Akt) and mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) signaling pathways were measured by western blotting. Energy metabolism of PTC cell lines was analyzed using a Seahorse Extracellular Flux analyzer.
Results: Three receptors could be detected in both PTC tissues and PTC cell lines. Expressions of IGF-1R and GLP-1R were more obvious in PTC than in normal thyroid cells. Neither insulin, four insulin analogs, and two GLP-1R agonists showed significant effects on the proliferation of PTC cells, nor did they influence the levels of Akt/p-Akt and Erk/p-Erk. None of these antidiabetic agents could change the mitochondrial respiration and glycolysis levels in PTC cell lines.
Conclusion: Both PTC tissues and the PTC cell lines express IR, IGF-1R, and GLP-1R. However, insulin analogs and GLP-1R agonists, which are commonly used to treat patients with diabetes, may not influence cell proliferation, the phosphoinositol-3 kinase/Akt and mitogen-activated protein kinase/Erk pathways, or energy metabolism in PTC cells. For now, it is not necessary to avoid use of these antidiabetic agents in patients with PTC.

Keywords: insulin analog, GLP-1R agonist, diabetes mellitus, papillary thyroid cancer

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