Leptin stimulates glucose uptake in C2C12 muscle cells by activation of ERK2.
Leptin regulates energy homeostasis via binding to receptors in the hypothalamus and peripheral tissues. We have investigated the signaling pathways and effects of leptin on glucose transport in C2C12 muscle cells. Long and short forms of leptin receptor are expressed in differentiated C2C12 myotubes. Leptin enhanced the DNA-binding activity of the transcription factor STAT3 and extracellular signal-regulated kinase 2 (ERK2) activity was stimulated by leptin after 15 min. Leptin increased glucose uptake and GLUT4 recruitment to the cell surface after 30 min, whereas no changes in GLUT1 was observed. PD98059, an ERK2 kinase-1 inhibitor, and wortmannin, an inhibitor of phosphatidylinositol 3-kinase blocked the leptin-induced increase in glucose uptake and GLUT4 recruitment to the cell surface. In contrast, insulin-stimulated glucose transport and GLUT4 translocation was inhibited by wortmannin, but not by PD98059. Our results suggest that leptin may regulate glucose metabolism by acting directly on skeletal muscle and that the signaling pathways involved may be different from that activated by insulin.
Berti
L
L
Department of Clinical Biochemistry, Glostrup Hospital, Denmark.
Gammeltoft
S
S
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006801:Humans; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000187:drug effects; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005419:Flavonoids; D005947:Glucose; D051275:Glucose Transporter Type 4; D020738:Leptin; D019950:Mitogen-Activated Protein Kinase 1; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D000077191:Wortmannin; C515448:LEPR protein, human; C495692:SLC2A4 protein, human; C494086:STAT3 protein, human; C495693:Slc2a4 protein, mouse; C494087:Stat3 protein, mouse; C515447:leptin receptor, mouse; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one