Thyroid stimulating hormone stimulates the expression of glucose transporter 2 via its receptor in pancreatic \u03b2 cell line, INS-1 cells

Jingya Lyu,Yasunori Sugiyama,Tomohiro Ibata,Fumi Kikuchi,Kazuko Yonezaki,Koji Murao,Tao Dong,Kensaku Fukunaga,Takuo Yoshimoto,Hitomi Imachi,Toshihiro Kobayashi,Seisuke Sato,Ryou Ishikawa,Hisakazu Iwama,Reiji Haba,Huanxiang Zhang,Nao Yamaji

doi:10.1038/s41598-018-20449-3

Jingya Lyu, Yasunori Sugiyama + Show 15 more

Open Access

https://doi.org/10.1038/s41598-018-20449-3

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Abstract

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.

Highlights

Thyroid stimulating hormone (TSH) stimulates the secretion of thyroid hormones by binding the TSH receptor (TSHR)
To confirm that TSHR is expressed in the rat pancreas, we used an antibody against the TSHR α subunit and detected a 62-kDa band in the rat pancreas, INS-1 cells, pancreatic islets isolated from rat and the rat thyroid (Fig. 1a–c)
Having confirmed that TSHR is expressed in rat pancreatic islets and in INS-1 cells, we used INS-1 cells to analyse the effects of TSH on the expression of pancreas-specific gene in pancreatic β cells

Summary

Introduction

Thyroid stimulating hormone (TSH) stimulates the secretion of thyroid hormones by binding the TSH receptor (TSHR). 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. Glucose transporter 2 (GLUT2), which is present within the plasma membrane of pancreatic β cells[8], plays an important role in glucose-induced insulin secretion from pancreatic β cells by catalyzing the uptake of glucose into the cell[9] It is a facilitative glucose transporter, and its expression is strongly reduced in glucose-unresponsive islets in various animal models of diabetes[9,10]. We evaluated the role of TSHR in regulating the expression of pancreas specific-genes including GLUT2 by the stimulation of TSH

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