Insulin hypersensitivity induced by hepatic PTEN gene ablation protects from murine endotoxemia.

Sepsis still remains a major cause for morbidity and mortality in patients. The molecular mechanisms underlying the disease are still enigmatic. A great number of therapeutic approaches have failed and treatment strategies are limited to date. Among those few admitted for clinical intervention, inte...

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Autores principales:	Philipp M Guenzl, Roman Raim, Julia Kral, Julia Brunner, Emine Sahin, Gernot Schabbauer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b6cb60e602e94748aeca94598049f074
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spelling	oai:doaj.org-article:b6cb60e602e94748aeca94598049f0742021-11-18T07:40:07ZInsulin hypersensitivity induced by hepatic PTEN gene ablation protects from murine endotoxemia.1932-620310.1371/journal.pone.0067013https://doaj.org/article/b6cb60e602e94748aeca94598049f0742013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23825606/?tool=EBIhttps://doaj.org/toc/1932-6203Sepsis still remains a major cause for morbidity and mortality in patients. The molecular mechanisms underlying the disease are still enigmatic. A great number of therapeutic approaches have failed and treatment strategies are limited to date. Among those few admitted for clinical intervention, intensive insulin treatment has proven to be effective in the reduction of disease related complications in critically ill patients. Insulin effectively reduces glucose levels and thereby contributes to protection. On the other hand insulin is a potent signaling pathway activator. One of those is the PI3K signaling axis. Activation of PI3K is known to limit pro-inflammatory gene expression. Here we can show that in a mouse model of insulin hypersensitivity induced by the deletion of the PI3K antagonist PTEN, specifically in hepatic tissue, significant protection is conferred in murine models of lethal endotoxemia and sepsis. Acute inflammatory responses are diminished, glucose metabolism normalized and vascular activation is reduced. Furthermore we investigated the hepatic gene expression profile of relevant anti-inflammatory genes in PTEN deficient mice and found marked upregulation of PPARγ and HO-1. We conclude from our data that insulin hypersensitivity via sustained activation of the PI3K signaling pathway exerts protective effects in acute inflammatory processes.Philipp M GuenzlRoman RaimJulia KralJulia BrunnerEmine SahinGernot SchabbauerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e67013 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Philipp M Guenzl Roman Raim Julia Kral Julia Brunner Emine Sahin Gernot Schabbauer Insulin hypersensitivity induced by hepatic PTEN gene ablation protects from murine endotoxemia.
description	Sepsis still remains a major cause for morbidity and mortality in patients. The molecular mechanisms underlying the disease are still enigmatic. A great number of therapeutic approaches have failed and treatment strategies are limited to date. Among those few admitted for clinical intervention, intensive insulin treatment has proven to be effective in the reduction of disease related complications in critically ill patients. Insulin effectively reduces glucose levels and thereby contributes to protection. On the other hand insulin is a potent signaling pathway activator. One of those is the PI3K signaling axis. Activation of PI3K is known to limit pro-inflammatory gene expression. Here we can show that in a mouse model of insulin hypersensitivity induced by the deletion of the PI3K antagonist PTEN, specifically in hepatic tissue, significant protection is conferred in murine models of lethal endotoxemia and sepsis. Acute inflammatory responses are diminished, glucose metabolism normalized and vascular activation is reduced. Furthermore we investigated the hepatic gene expression profile of relevant anti-inflammatory genes in PTEN deficient mice and found marked upregulation of PPARγ and HO-1. We conclude from our data that insulin hypersensitivity via sustained activation of the PI3K signaling pathway exerts protective effects in acute inflammatory processes.
format	article
author	Philipp M Guenzl Roman Raim Julia Kral Julia Brunner Emine Sahin Gernot Schabbauer
author_facet	Philipp M Guenzl Roman Raim Julia Kral Julia Brunner Emine Sahin Gernot Schabbauer
author_sort	Philipp M Guenzl
title	Insulin hypersensitivity induced by hepatic PTEN gene ablation protects from murine endotoxemia.
title_short	Insulin hypersensitivity induced by hepatic PTEN gene ablation protects from murine endotoxemia.
title_full	Insulin hypersensitivity induced by hepatic PTEN gene ablation protects from murine endotoxemia.
title_fullStr	Insulin hypersensitivity induced by hepatic PTEN gene ablation protects from murine endotoxemia.
title_full_unstemmed	Insulin hypersensitivity induced by hepatic PTEN gene ablation protects from murine endotoxemia.
title_sort	insulin hypersensitivity induced by hepatic pten gene ablation protects from murine endotoxemia.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b6cb60e602e94748aeca94598049f074
work_keys_str_mv	AT philippmguenzl insulinhypersensitivityinducedbyhepaticptengeneablationprotectsfrommurineendotoxemia AT romanraim insulinhypersensitivityinducedbyhepaticptengeneablationprotectsfrommurineendotoxemia AT juliakral insulinhypersensitivityinducedbyhepaticptengeneablationprotectsfrommurineendotoxemia AT juliabrunner insulinhypersensitivityinducedbyhepaticptengeneablationprotectsfrommurineendotoxemia AT eminesahin insulinhypersensitivityinducedbyhepaticptengeneablationprotectsfrommurineendotoxemia AT gernotschabbauer insulinhypersensitivityinducedbyhepaticptengeneablationprotectsfrommurineendotoxemia
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Insulin hypersensitivity induced by hepatic PTEN gene ablation protects from murine endotoxemia.

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