Hepatocyte growth factor is a novel stimulator of glucose uptake and metabolism in skeletal muscle cells.
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.
Perdomo
German
G
Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Martinez-Brocca
Maria A
MA
Bhatt
Bankim A
BA
Brown
Nicholas F
NF
O'Doherty
Robert M
RM
Garcia-Ocaña
Adolfo
A
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats
D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose