Berti L, Gammeltoft S
Department of Clinical Biochemistry, Glostrup Hospital, Denmark.
Mol Cell Endocrinol. 1999 Nov 25;157(1-2):121-30. doi: 10.1016/s0303-7207(99)00154-9.
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.
瘦素通过与下丘脑和外周组织中的受体结合来调节能量平衡。我们研究了瘦素在C2C12肌肉细胞中对葡萄糖转运的信号通路和影响。在分化的C2C12肌管中表达了长型和短型瘦素受体。瘦素增强了转录因子STAT3的DNA结合活性，并且在15分钟后瘦素刺激了细胞外信号调节激酶2（ERK2）的活性。30分钟后，瘦素增加了葡萄糖摄取以及GLUT4向细胞表面的募集，而未观察到GLUT1有变化。ERK2激酶-1抑制剂PD98059和磷脂酰肌醇3激酶抑制剂渥曼青霉素阻断了瘦素诱导的葡萄糖摄取增加以及GLUT4向细胞表面的募集。相反，渥曼青霉素抑制了胰岛素刺激的葡萄糖转运和GLUT4易位，但PD98059没有。我们的结果表明，瘦素可能通过直接作用于骨骼肌来调节葡萄糖代谢，并且所涉及的信号通路可能与胰岛素激活的信号通路不同。
