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

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.