A Hepatocyte Growth Factor Receptor (Met)–Insulin Receptor hybrid governs hepatic glucose metabolism

Met is the transmembrane tyrosine kinase cell surface receptor for Hepatocyte Growth Factor (HGF) and is related to the insulin receptor (INSR) tyrosine kinase. Here we report that the HGF–Met axis controls metabolism by stimulating hepatic glucose uptake and suppressing hepatic glucose output. We s...

Descripción completa

Detalles Bibliográficos
Autores principales: Fafalios, Arlee, Ma, Jihong, Tan, Xinping, Stoops, John, Luo, Jianhua, DeFrances, Marie C., Zarnegar, Reza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233634/
https://www.ncbi.nlm.nih.gov/pubmed/22081023
http://dx.doi.org/10.1038/nm.2531
_version_ 1782218445211828224
author Fafalios, Arlee
Ma, Jihong
Tan, Xinping
Stoops, John
Luo, Jianhua
DeFrances, Marie C.
Zarnegar, Reza
author_facet Fafalios, Arlee
Ma, Jihong
Tan, Xinping
Stoops, John
Luo, Jianhua
DeFrances, Marie C.
Zarnegar, Reza
author_sort Fafalios, Arlee
collection PubMed
description Met is the transmembrane tyrosine kinase cell surface receptor for Hepatocyte Growth Factor (HGF) and is related to the insulin receptor (INSR) tyrosine kinase. Here we report that the HGF–Met axis controls metabolism by stimulating hepatic glucose uptake and suppressing hepatic glucose output. We show that Met is essential for an optimum hepatic insulin response; Met exerts this by virtue of directly engaging the insulin receptor (INSR) in a Met–INSR hybrid complex. We found that the HGF–Met system restores insulin responsiveness in a mouse model of insulin refractoriness. The results provide new insights into the molecular basis of hepatic insulin resistance and suggest that HGF may have therapeutic potential in the clinical setting of type 2 diabetes.
format Online
Article
Text
id pubmed-3233634
institution National Center for Biotechnology Information
language English
publishDate 2011
record_format MEDLINE/PubMed
spelling pubmed-32336342012-06-01 A Hepatocyte Growth Factor Receptor (Met)–Insulin Receptor hybrid governs hepatic glucose metabolism Fafalios, Arlee Ma, Jihong Tan, Xinping Stoops, John Luo, Jianhua DeFrances, Marie C. Zarnegar, Reza Nat Med Article Met is the transmembrane tyrosine kinase cell surface receptor for Hepatocyte Growth Factor (HGF) and is related to the insulin receptor (INSR) tyrosine kinase. Here we report that the HGF–Met axis controls metabolism by stimulating hepatic glucose uptake and suppressing hepatic glucose output. We show that Met is essential for an optimum hepatic insulin response; Met exerts this by virtue of directly engaging the insulin receptor (INSR) in a Met–INSR hybrid complex. We found that the HGF–Met system restores insulin responsiveness in a mouse model of insulin refractoriness. The results provide new insights into the molecular basis of hepatic insulin resistance and suggest that HGF may have therapeutic potential in the clinical setting of type 2 diabetes. 2011-11-13 /pmc/articles/PMC3233634/ /pubmed/22081023 http://dx.doi.org/10.1038/nm.2531 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Fafalios, Arlee
Ma, Jihong
Tan, Xinping
Stoops, John
Luo, Jianhua
DeFrances, Marie C.
Zarnegar, Reza
A Hepatocyte Growth Factor Receptor (Met)–Insulin Receptor hybrid governs hepatic glucose metabolism
title A Hepatocyte Growth Factor Receptor (Met)–Insulin Receptor hybrid governs hepatic glucose metabolism
title_full A Hepatocyte Growth Factor Receptor (Met)–Insulin Receptor hybrid governs hepatic glucose metabolism
title_fullStr A Hepatocyte Growth Factor Receptor (Met)–Insulin Receptor hybrid governs hepatic glucose metabolism
title_full_unstemmed A Hepatocyte Growth Factor Receptor (Met)–Insulin Receptor hybrid governs hepatic glucose metabolism
title_short A Hepatocyte Growth Factor Receptor (Met)–Insulin Receptor hybrid governs hepatic glucose metabolism
title_sort hepatocyte growth factor receptor (met)–insulin receptor hybrid governs hepatic glucose metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233634/
https://www.ncbi.nlm.nih.gov/pubmed/22081023
http://dx.doi.org/10.1038/nm.2531
work_keys_str_mv AT fafaliosarlee ahepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT majihong ahepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT tanxinping ahepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT stoopsjohn ahepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT luojianhua ahepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT defrancesmariec ahepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT zarnegarreza ahepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT fafaliosarlee hepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT majihong hepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT tanxinping hepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT stoopsjohn hepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT luojianhua hepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT defrancesmariec hepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism
AT zarnegarreza hepatocytegrowthfactorreceptormetinsulinreceptorhybridgovernshepaticglucosemetabolism

Ejemplares similares