A hepatocyte growth factor receptor (Met)-insulin receptor hybrid governs hepatic glucose metabolism

被引：95

作者：

Fafalios, Arlee ^{[1
]}

Ma, Jihong ^{[1
]}

Tan, Xinping ^{[1
]}

Stoops, John ^{[1
]}

Luo, Jianhua ^{[1
]}

DeFrances, Marie C. ^{[1
,2
,3
]}

Zarnegar, Reza ^{[1
,2
,3
]}

机构：

[1] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA

[2] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA

[3] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA

来源：

NATURE MEDICINE | 2011年 / 17卷 / 12期

基金：

美国国家卫生研究院;

关键词：

INDUCED FATTY LIVER; UP-REGULATION; C-MET; MICE; REGENERATION; PATHWAY; IRS-2; RATS; FAS;

D O I：

10.1038/nm.2531

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Met is the transmembrane tyrosine kinase cell surface receptor for hepatocyte growth factor (HGF) and is structurally related to the insulin receptor (INSR) tyrosine kinase. Here we report that the HGF-Met axis regulates metabolism by stimulating hepatic glucose uptake and suppressing hepatic glucose output. We show that Met is essential for an optimal hepatic insulin response by directly engaging INSR to form a Met-INSR hybrid complex, which culminates in a robust signal output. We also found that the HGF-Met system restores insulin responsiveness in a mouse model of insulin refractoriness. These results provide new insights into the molecular basis of hepatic insulin resistance and suggest that HGF may have therapeutic potential for type 2 diabetes in the clinical setting.

引用

页码：1577 / U87

页数：9

共 28 条

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