Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2–YY1 signaling pathway

Abstract Growth hormone (GH) is one of the critical factors in maintaining glucose metabolism. B-cell translocation gene 2 (BTG2) and yin yang 1 (YY1) are key regulators of diverse metabolic processes. In this study, we investigated the link between GH and BTG2–YY1 signaling pathway in glucose metab...

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Autores principales:	Jeong-Rang Jo, Seungwon An, Swati Ghosh, Balachandar Nedumaran, Yong Deuk Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/605a9caf04d54ab491219e4a168bc9e3
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spelling	oai:doaj.org-article:605a9caf04d54ab491219e4a168bc9e32021-12-02T17:27:19ZGrowth hormone promotes hepatic gluconeogenesis by enhancing BTG2–YY1 signaling pathway10.1038/s41598-021-98537-02045-2322https://doaj.org/article/605a9caf04d54ab491219e4a168bc9e32021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98537-0https://doaj.org/toc/2045-2322Abstract Growth hormone (GH) is one of the critical factors in maintaining glucose metabolism. B-cell translocation gene 2 (BTG2) and yin yang 1 (YY1) are key regulators of diverse metabolic processes. In this study, we investigated the link between GH and BTG2–YY1 signaling pathway in glucose metabolism. GH treatment elevated the expression of hepatic Btg2 and Yy1 in primary mouse hepatocytes and mouse livers. Glucose production in primary mouse hepatocytes and serum blood glucose levels were increased during GH exposure. Overexpression of hepatic Btg2 and Yy1 induced key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6 phosphatase (G6PC) as well as glucose production in primary mouse hepatocytes, whereas this phenomenon was markedly diminished by knockdown of Btg2 and Yy1. Here, we identified the YY1-binding site on the Pck1 and G6pc gene promoters using reporter assays and point mutation analysis. The regulation of hepatic gluconeogenic genes induced by GH treatment was clearly linked with YY1 recruitment on gluconeogenic gene promoters. Overall, this study demonstrates that BTG2 and YY1 are novel regulators of GH-dependent regulation of hepatic gluconeogenic genes and glucose production. BTG2 and YY1 may be crucial therapeutic targets to intervene in metabolic dysfunction in response to the GH-dependent signaling pathway.Jeong-Rang JoSeungwon AnSwati GhoshBalachandar NedumaranYong Deuk KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeong-Rang Jo Seungwon An Swati Ghosh Balachandar Nedumaran Yong Deuk Kim Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2–YY1 signaling pathway
description	Abstract Growth hormone (GH) is one of the critical factors in maintaining glucose metabolism. B-cell translocation gene 2 (BTG2) and yin yang 1 (YY1) are key regulators of diverse metabolic processes. In this study, we investigated the link between GH and BTG2–YY1 signaling pathway in glucose metabolism. GH treatment elevated the expression of hepatic Btg2 and Yy1 in primary mouse hepatocytes and mouse livers. Glucose production in primary mouse hepatocytes and serum blood glucose levels were increased during GH exposure. Overexpression of hepatic Btg2 and Yy1 induced key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6 phosphatase (G6PC) as well as glucose production in primary mouse hepatocytes, whereas this phenomenon was markedly diminished by knockdown of Btg2 and Yy1. Here, we identified the YY1-binding site on the Pck1 and G6pc gene promoters using reporter assays and point mutation analysis. The regulation of hepatic gluconeogenic genes induced by GH treatment was clearly linked with YY1 recruitment on gluconeogenic gene promoters. Overall, this study demonstrates that BTG2 and YY1 are novel regulators of GH-dependent regulation of hepatic gluconeogenic genes and glucose production. BTG2 and YY1 may be crucial therapeutic targets to intervene in metabolic dysfunction in response to the GH-dependent signaling pathway.
format	article
author	Jeong-Rang Jo Seungwon An Swati Ghosh Balachandar Nedumaran Yong Deuk Kim
author_facet	Jeong-Rang Jo Seungwon An Swati Ghosh Balachandar Nedumaran Yong Deuk Kim
author_sort	Jeong-Rang Jo
title	Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2–YY1 signaling pathway
title_short	Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2–YY1 signaling pathway
title_full	Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2–YY1 signaling pathway
title_fullStr	Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2–YY1 signaling pathway
title_full_unstemmed	Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2–YY1 signaling pathway
title_sort	growth hormone promotes hepatic gluconeogenesis by enhancing btg2–yy1 signaling pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/605a9caf04d54ab491219e4a168bc9e3
work_keys_str_mv	AT jeongrangjo growthhormonepromoteshepaticgluconeogenesisbyenhancingbtg2yy1signalingpathway AT seungwonan growthhormonepromoteshepaticgluconeogenesisbyenhancingbtg2yy1signalingpathway AT swatighosh growthhormonepromoteshepaticgluconeogenesisbyenhancingbtg2yy1signalingpathway AT balachandarnedumaran growthhormonepromoteshepaticgluconeogenesisbyenhancingbtg2yy1signalingpathway AT yongdeukkim growthhormonepromoteshepaticgluconeogenesisbyenhancingbtg2yy1signalingpathway
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Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2–YY1 signaling pathway

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