Abstract
Hyperthyroidism can cause glucose metabolism disorders and insulin resistance. Insulin resistance in muscle and adipose tissues has been extensively studied, whereas investigations on β-cell insulin resistance are limited. This study preliminarily explored the effects of high T3 levels on β-cell line (MIN6) insulin resistance, as well as the roles of endoplasmic reticulum stress (ERS). In this study, we treated β-cell line with T3, with or without an inhibitor of phosphotyrosine phosphatases (PTPs, sodium vanadate) or ERS inhibitor (4-PBA). The results indicated that high levels of T3 significantly inhibited insulin secretion in β-cell line. In addition, we observed an upregulation of p-IRS-1ser307 and downregulation of Akt. These results can be corrected by sodium vanadate. Moreover, high T3 levels upregulate the ERS-related proteins PERK, IRE1, ATF6, and GRP78, as well as ERS-related apoptosis CHOP and caspase-12. Similarly, this change can be corrected by 4-PBA. These results suggest that high T3 levels can induce insulin resistance in β-cell line by activating ERS and the apoptotic pathway.
Highlights
About 70% to 75% of hyperthyroidism cases are associated with glucose metabolism disorders and insulin resistance [1, 2]
This change can be corrected by 4-PBA. These results suggest that high T3 levels can induce insulin resistance in β-cell line by activating endoplasmic reticulum stress (ERS) and the apoptotic pathway
Cell viability of MIN6 added by different T3 concentrations
Summary
About 70% to 75% of hyperthyroidism cases are associated with glucose metabolism disorders and insulin resistance [1, 2]. The effect of thyroid hormones on glucose metabolism is mainly through T3, which binds to T3 receptors in β-cell nuclei and regulates insulin signal transduction as well as secretion [3, 4]. A variety of adverse factors can block the synthesis and processing of proteins, such as chemical toxicants, high glucose, low temperature, and hypoxia [6]. These factors can cause unfolded or misfolded proteins to accumulate in the ER cavity and induce endoplasmic reticulum stress (ERS) [7, 8]. A growing body of evidence suggests that insulin resistance in β-cells induced by ERS affects insulin signal transduction [9, 10]. The purpose of this study was to investigate the effects of high T3 levels on insulin signal transduction, insulin secretion in β-cells, and the role of ERS in this process
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