Liang Bo, Liu Liyun, Huang Huibin, Li Liangyi, Zhou Jingxiong
Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China.
Department of Pediatrics, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou 350005, China.
Mediators Inflamm. 2020 Jul 22;2020:5287108. doi: 10.1155/2020/5287108. eCollection 2020.
Hyperthyroidism can cause glucose metabolism disorders and insulin resistance. Insulin resistance in muscle and adipose tissues has been extensively studied, whereas investigations on -cell insulin resistance are limited. This study preliminarily explored the effects of high T3 levels on -cell line (MIN6) insulin resistance, as well as the roles of endoplasmic reticulum stress (ERS). In this study, we treated -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 -cell line. In addition, we observed an upregulation of p-IRS-1 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 -cell line by activating ERS and the apoptotic pathway.
甲状腺功能亢进可导致糖代谢紊乱和胰岛素抵抗。肌肉和脂肪组织中的胰岛素抵抗已得到广泛研究，而关于β细胞胰岛素抵抗的研究有限。本研究初步探讨了高T3水平对β细胞系（MIN6）胰岛素抵抗的影响，以及内质网应激（ERS）的作用。在本研究中，我们用T3处理β细胞系，同时使用或不使用磷酸酪氨酸磷酸酶（PTPs，钒酸钠）抑制剂或ERS抑制剂（4-苯基丁酸）。结果表明，高水平的T3显著抑制β细胞系中的胰岛素分泌。此外，我们观察到p-IRS-1上调和Akt下调。这些结果可通过钒酸钠纠正。此外，高T3水平上调了与ERS相关的蛋白质PERK、IRE1、ATF6和GRP78，以及与ERS相关的凋亡蛋白CHOP和caspase-12。同样，这种变化可通过4-苯基丁酸纠正。这些结果表明，高T3水平可通过激活ERS和凋亡途径诱导β细胞系中的胰岛素抵抗。
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