Bates S H, Gardiner J V, Jones R B, Bloom S R, Bailey C J
School of Life and Health Sciences, Aston University, Birmingham, UK.
Horm Metab Res. 2002 Mar;34(3):111-5. doi: 10.1055/s-2002-23192.
The adipocyte hormone, leptin, acts via the central nervous system to modulate glucose metabolism by skeletal muscle, but the direct effects of leptin on glucose metabolism by skeletal muscle are unclear. In this study, we have examined effects of leptin on glucose uptake by cultured L6 muscle cells assessed with the non-metabolised glucose analogue 2-deoxy-D-glucose. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of RNA showed that L6 muscle cells express a short isoform of the leptin receptor (ObRa), but not the long isoform (ObRb). In the absence of added insulin, incubation of L6 muscle cells with murine leptin (10( -11)-10( -8) M) for 10 min and 1 h increased glucose uptake by 15 % - 23 %. This effect of leptin was lost by 4 h. Leptin (10( -10) - 10( -9) M) initially (after 10 min) suppressed insulin-stimulated glucose uptake by 14 - 16 %, but had no effect in the longer term. Leptin-stimulated glucose uptake was inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, but not by the janus kinase-2 (JAK-2) inhibitor tyrphostin AG490. The results suggest that leptin can act directly on L6 muscle cellsvia a short leptin receptor isoform to acutely stimulate basal (but not insulin-stimulated) glucose uptake via a PI3K-dependent pathway.
脂肪细胞激素瘦素通过中枢神经系统作用，调节骨骼肌的葡萄糖代谢，但瘦素对骨骼肌葡萄糖代谢的直接作用尚不清楚。在本研究中，我们用非代谢性葡萄糖类似物2-脱氧-D-葡萄糖评估了瘦素对培养的L6肌肉细胞葡萄糖摄取的影响。RNA的逆转录聚合酶链反应（RT-PCR）分析表明，L6肌肉细胞表达瘦素受体的短异构体（ObRa），而不表达长异构体（ObRb）。在不添加胰岛素的情况下，将L6肌肉细胞与小鼠瘦素（10^(-11)-10^(-8) M）孵育10分钟和1小时，葡萄糖摄取增加了15%-23%。4小时后，瘦素的这种作用消失。瘦素（10^(-10)-10^(-9) M）最初（10分钟后）使胰岛素刺激的葡萄糖摄取抑制了14%-16%，但长期来看没有影响。磷脂酰肌醇3激酶（PI3K）抑制剂渥曼青霉素可抑制瘦素刺激的葡萄糖摄取，而Janus激酶-2（JAK-2）抑制剂 tyrphostin AG490则无此作用。结果表明，瘦素可通过短的瘦素受体异构体直接作用于L6肌肉细胞，通过PI3K依赖途径急性刺激基础（而非胰岛素刺激）葡萄糖摄取。
