Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
Department of Cell Biology, Medical College of Soochow University, Jiangsu Key Laboratory of Stem Cell Research, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China.
Sci Rep. 2018 Jan 31;8(1):1986. doi: 10.1038/s41598-018-20449-3.
Thyroid stimulating hormone (TSH) stimulates the secretion of thyroid hormones by binding the TSH receptor (TSHR). TSHR is well-known to be expressed in thyroid tissue, excepting it, TSHR has also been expressed in many other tissues. In this study, we have examined the expression of TSHR in rat pancreatic islets and evaluated the role of TSH in regulating pancreas-specific gene expression. TSHR was confirmed to be expressed in rodent pancreatic islets and its cell line, INS-1 cells. TSH directly affected the glucose uptake in INS cells by up-regulating the expression of GLUT2, and furthermore this process was blocked by SB203580, the specific inhibitor of the p38 MAPK signaling pathway. Similarly, TSH stimulated GLUT2 promoter activity, while both a dominant-negative p38MAPK α isoform (p38MAPK α-DN) and the specific inhibitor for p38MAPK α abolished the stimulatory effect of TSH on GLUT2 promoter activity. Finally, INS-1 cells treated with TSH showed increased protein level of glucokinase and enhanced glucose-stimulated insulin secretion. Together, these results confirm that TSHR is expressed in INS-1 cells and rat pancreatic islets, and suggest that activation of the p38MAPK α might be required for TSH-induced GLUT2 gene transcription in pancreatic β cells.
促甲状腺激素(TSH)通过与 TSH 受体(TSHR)结合来刺激甲状腺激素的分泌。TSHR 已知在甲状腺组织中表达,除了甲状腺组织外,TSHR 还在许多其他组织中表达。在这项研究中,我们检查了 TSHR 在大鼠胰岛中的表达,并评估了 TSH 在调节胰腺特异性基因表达中的作用。在啮齿动物胰岛和其细胞系 INS-1 细胞中证实了 TSHR 的表达。TSH 通过上调 GLUT2 的表达直接影响 INS 细胞中的葡萄糖摄取,并且该过程被 p38MAPK 信号通路的特异性抑制剂 SB203580 阻断。同样,TSH 刺激 GLUT2 启动子活性,而显性失活的 p38MAPK α 同工型(p38MAPK α-DN)和 p38MAPK α 的特异性抑制剂均消除了 TSH 对 GLUT2 启动子活性的刺激作用。最后,用 TSH 处理的 INS-1 细胞显示葡萄糖激酶的蛋白水平增加,并增强了葡萄糖刺激的胰岛素分泌。总之,这些结果证实 TSHR 在 INS-1 细胞和大鼠胰岛中表达,并表明 p38MAPK α 的激活可能是 TSH 诱导胰腺β 细胞中 GLUT2 基因转录所必需的。