Hepatocyte Growth Factor Is a Novel Stimulator of Glucose Uptake and Metabolism in Skeletal Muscle Cells

Abstract

Skeletal muscle plays a major role in glucose and lipid metabolism. Active hepatocyte growth factor (HGF) is present in the extracellular matrix in skeletal muscle. However, the effects of HGF on glucose and lipid metabolism in skeletal muscle are completely unknown. We therefore examined the effects of HGF on deoxyglucose uptake (DOGU), glucose utilization, and fatty acid oxidation (FAO) in skeletal muscle cells. HGF significantly enhanced DOGU in mouse soleus muscles in vitro. Furthermore, HGF significantly increased: (i) DOGU in a time-and dose-dependent manner; (ii) glucose utilization; and (iii) plasma membrane expression of Glut-1 and Glut-4 in the rat skeletal muscle model of L6 myotubes. HGF-mediated effect on DOGU was dependent on the activation of phosphatidylinositol 3-kinase signaling pathway. On the other hand, HGF markedly and significantly decreased FAO in L6 myotubes without affecting the activities of carnitine palmitoyltransferase I and II. Collectively, these results indicate that HGF is a potent activator of glucose transport and metabolism and also a strong inhibitor of FAO in rodent myotubes. HGF, through its ability to stimulate glucose transport and metabolism and to impair FAO, may participate in the regulation of glucose disposal in skeletal muscle.

Interleukin‐6 promotes 2‐deoxyglucose uptake through p44/42 MAPKs activation via Ca2+/PKC and EGF receptor in primary cultured chicken hepatocytes

“…We also observed that the hepatocytes treated with PI3K-specific siRNA and a Akt inhibitor blocked the IL-6-induced increase in GLUT-2 expression and 2-DG uptake which strongly suggests the involvement of PI3K/Akt pathway. Consistently, Perdomo et al (2008) reported that GLUT-4 translocation to the plasma membrane is abolished by wortmannin (PI3K inhibitor) and Akt inhibitor. Recent evidence suggests a link between IL-6 and MAPKs.…”

Decorin Induces Mitophagy in Breast Carcinoma Cells via Peroxisome Proliferator-activated Receptor γ Coactivator-1α (PGC-1α) and Mitostatin

“…However, in the context of tumor mitochondrial physiology, suppression of downstream complexes is more consistent with inhibiting biosynthetic pathways necessary for tumorigenic growth. Interestingly, HGF/Met signaling augments glycolytic flux (77); however, we show a significant enhancement of OXPHOS components, potentially to support the cell with increased biosynthetic abilities consummate with the pro-proliferative and pro-angiogenic nature of HGF/Met signaling. These data substantiate a novel anti-tumorigenic role for decorin to compromise mitochondrial capacity (and potentially function) through the concerted suppression of multiple key components of OXPHOS (Fig.…”

HGF-induced invasion by prostate tumor cells requires anterograde lysosome trafficking and activity of Na+-H+ exchangers

“…Growth factors, including HGF, EGF and TNF-, have been shown to increase glucose utilization in a variety of cells (Bertola et al, 2007;Boussouar and Benahmed, 1999;Hsu and Sabatini, 2008;Perdomo et al, 2008;Véga et al, 2002). Furthermore, Kaplan and colleagues (Kaplan et al, 2000) have shown that HGF also enhances glycolysis and oxidative phosphorylation in murine mammary cells.…”