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Updated: May 27, 2026

Live-Cell Förster Resonance Energy Transfer Imaging of Metabolically Regulated Akt Activation Dynamics in HepG2 Cells
Published on: May 23, 2025
A hepatocyte growth factor receptor (Met)-insulin receptor hybrid governs hepatic glucose metabolism
Arlee Fafalios1, Jihong Ma, Xinping Tan
1Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract:
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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