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

First Author  Fafalios A Year  2011
Journal  Nat Med Volume  17
Issue  12 Pages  1577-84
PubMed ID  22081023 Mgi Jnum  J:180206
Mgi Id  MGI:5305857 Doi  10.1038/nm.2531
Citation  Fafalios A, et al. (2011) A hepatocyte growth factor receptor (Met)-insulin receptor hybrid governs hepatic glucose metabolism. Nat Med 17(12):1577-84
abstractText  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.
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