Insulin upregulates betatrophin expression via PI3K/Akt pathway

Abstract Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Puhan Lu, Xi Chen, Zeqing Zhang, Jianhua Zhang, Yan Yang, Zhelong Liu, Junhui Xie, Shiying Shao, Xinrong Zhou, Shuhong Hu, Wentao He, Jiajun Zhao, Xuefeng Yu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6af472a0bd544116b7a8ee9e96d1a57b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6af472a0bd544116b7a8ee9e96d1a57b
record_format	dspace
spelling	oai:doaj.org-article:6af472a0bd544116b7a8ee9e96d1a57b2021-12-02T15:05:39ZInsulin upregulates betatrophin expression via PI3K/Akt pathway10.1038/s41598-017-06052-y2045-2322https://doaj.org/article/6af472a0bd544116b7a8ee9e96d1a57b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06052-yhttps://doaj.org/toc/2045-2322Abstract Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group. These results suggest that it is insulin, not IR that promotes betatrophin expression. In the meantime, PI3K/Akt pathway was activated by insulin and suppressed by above agents that caused IR. Insulin-upregulated betatrophin expression was suppressed by PI3K/Akt inhibitors and IR, suggesting that insulin upregulates and IR decreases betatrophin production through PI3K/Akt pathway. Consistently, the treatment of insulin in mice dose-dependently upregulated betatrophin levels, and the administration of metformin in IR mice also stimulated betatrophin production since published study showed metformin improved PI3K/Akt pathway and IR. In humans, compared with those without insulin treatment, serum betatrophin levels were increased in type 2 diabetic patients with insulin treatment. In conclusion, insulin stimulates betatrophin secretion through PI3K/Akt pathway and IR may play an opposite role.Puhan LuXi ChenZeqing ZhangJianhua ZhangYan YangZhelong LiuJunhui XieShiying ShaoXinrong ZhouShuhong HuWentao HeJiajun ZhaoXuefeng YuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Puhan Lu Xi Chen Zeqing Zhang Jianhua Zhang Yan Yang Zhelong Liu Junhui Xie Shiying Shao Xinrong Zhou Shuhong Hu Wentao He Jiajun Zhao Xuefeng Yu Insulin upregulates betatrophin expression via PI3K/Akt pathway
description	Abstract Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group. These results suggest that it is insulin, not IR that promotes betatrophin expression. In the meantime, PI3K/Akt pathway was activated by insulin and suppressed by above agents that caused IR. Insulin-upregulated betatrophin expression was suppressed by PI3K/Akt inhibitors and IR, suggesting that insulin upregulates and IR decreases betatrophin production through PI3K/Akt pathway. Consistently, the treatment of insulin in mice dose-dependently upregulated betatrophin levels, and the administration of metformin in IR mice also stimulated betatrophin production since published study showed metformin improved PI3K/Akt pathway and IR. In humans, compared with those without insulin treatment, serum betatrophin levels were increased in type 2 diabetic patients with insulin treatment. In conclusion, insulin stimulates betatrophin secretion through PI3K/Akt pathway and IR may play an opposite role.
format	article
author	Puhan Lu Xi Chen Zeqing Zhang Jianhua Zhang Yan Yang Zhelong Liu Junhui Xie Shiying Shao Xinrong Zhou Shuhong Hu Wentao He Jiajun Zhao Xuefeng Yu
author_facet	Puhan Lu Xi Chen Zeqing Zhang Jianhua Zhang Yan Yang Zhelong Liu Junhui Xie Shiying Shao Xinrong Zhou Shuhong Hu Wentao He Jiajun Zhao Xuefeng Yu
author_sort	Puhan Lu
title	Insulin upregulates betatrophin expression via PI3K/Akt pathway
title_short	Insulin upregulates betatrophin expression via PI3K/Akt pathway
title_full	Insulin upregulates betatrophin expression via PI3K/Akt pathway
title_fullStr	Insulin upregulates betatrophin expression via PI3K/Akt pathway
title_full_unstemmed	Insulin upregulates betatrophin expression via PI3K/Akt pathway
title_sort	insulin upregulates betatrophin expression via pi3k/akt pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6af472a0bd544116b7a8ee9e96d1a57b
work_keys_str_mv	AT puhanlu insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT xichen insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT zeqingzhang insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT jianhuazhang insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT yanyang insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT zhelongliu insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT junhuixie insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT shiyingshao insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT xinrongzhou insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT shuhonghu insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT wentaohe insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT jiajunzhao insulinupregulatesbetatrophinexpressionviapi3kaktpathway AT xuefengyu insulinupregulatesbetatrophinexpressionviapi3kaktpathway
_version_	1718388770727788544

Insulin upregulates betatrophin expression via PI3K/Akt pathway

Ejemplares similares