Thyroid stimulating hormone stimulates the expression of glucose transporter 2 via its receptor in pancreatic β cell line, INS-1 cells.
Thyroid stimulating hormone stimulates the expression of glucose transporter 2 via its receptor in pancreatic β cell line, INS-1 cells.
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DOI：
10.1038/s41598-018-20449-3
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发表时间：
2018-01-31
影响因子：
4.6
通讯作者：
Murao K
中科院分区：
文献类型：
--
作者：
Lyu J;Imachi H;Yoshimoto T;Fukunaga K;Sato S;Ibata T;Kobayashi T;Dong T;Yonezaki K;Yamaji N;Kikuchi F;Iwama H;Ishikawa R;Haba R;Sugiyama Y;Zhang H;Murao K
促甲状腺激素（TSH）通过结合促甲状腺激素受体（TSHR）刺激甲状腺激素的分泌。众所周知，TSHR主要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。在本研究中，我们检测了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。证实TSHR在啮齿动物胰岛及其细胞系INS-1细胞中表达。TSH通过上调GLUT2的表达直接影响INS细胞的葡萄糖摄取，并且这一过程被p38 MAPK信号通路特异性抑制剂SB203580阻断。同样，TSH刺激了GLUT2启动子活性，而p38MAPK α的显性阴性亚型（p38MAPK α- dn）和p38MAPK α的特异性抑制剂都消除了TSH对GLUT2启动子活性的刺激作用。最后，经TSH处理的INS-1细胞显示葡萄糖激酶蛋白水平升高，葡萄糖刺激的胰岛素分泌增强。总之，这些结果证实了TSHR在INS-1细胞和大鼠胰岛中表达，并提示p38MAPK α的激活可能是tsh诱导的胰β细胞中GLUT2基因转录所必需的。
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.
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影响因子：
4.1
作者：
Lin, Jianguo;Chen, Anping
通讯作者：
Chen, Anping
影响因子：
4.8
作者：
Enslen, H;Raingeaud, J;Davis, RJ
通讯作者：
Davis, RJ
影响因子：
0.2
作者：
Kapadia KB;Bhatt PA;Shah JS
通讯作者：
Shah JS
影响因子：
2.2
作者：
JAP, TS;HO, LT;WON, JGS
通讯作者：
WON, JGS
DOI：
10.1073/pnas.95.21.12317
发表时间：
1998-10-13
影响因子：
11.1
作者：
Guillam, MT;Burcelin, R;Thorens, B
通讯作者：
Thorens, B