Leptin stimulates glucose uptake in C2C12 muscle cells by activation of ERK2

Leptin regulates energy homeostasis via binding to receptors in the hypotha lamus and peripheral tissues. We have investigated the signaling pathways a nd effects of leptin on glucose transport in C2C12 muscle cells. Long and s hort forms of leptin receptor are expressed in differentiated C2C12 myotube s. Leptin enhanced the DNA-binding activity of the transcription factor STA T3 and extracellular signal regulated kinase 2 (ERK2) activity was stimulat ed by leptin after 15 min. Leptin increased glucose uptake and GLUT4 recrui tment to the cell surface after 30 min, whereas no changes in GLUT1 was obs erved. PD98059, an ERK2 kinase-l inhibitor, and wortmannin, an inhibitor of phosphatidylinositol 3-kinase blocked the leptin-induced increase in gluco se uptake and GLUT4 recruitment to the cell surface. In contrast, insulin-s timulated glucose transport and GLUT4 translocation was inhibited by wortma nnin, but not by PD98059. Our results suggest that leptin may regulate gluc ose metabolism by acting directly on skeletal muscle and that the signaling pathways involved may be different from that activated by insulin. (C) 199 9 Elsevier Science Ireland Ltd. All rights reserved.