Acute stimulation of glucose uptake by leptin in L6 muscle cells
Acute stimulation of glucose uptake by leptin in L6 muscle cells
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DOI：
10.1055/s-2002-23192
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发表时间：
2002-03-01
影响因子：
2.2
通讯作者：
Bailey, CJ
中科院分区：
文献类型：
--
作者：
Bates, SH;Gardiner, JV;Bailey, CJ
瘦素是一种脂肪细胞激素，通过中枢神经系统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影响尚不清楚。在这项研究中，我们用非代谢葡萄糖类似物2-脱氧-D-葡萄糖评估了瘦素对培养的L6肌细胞葡萄糖摄取的影响。逆转录聚合酶链式反应(RT-PCR)分析表明，L6肌肉细胞表达瘦素受体的短亚型(Obra)，而不表达长亚型(ObRb)。在没有添加胰岛素的情况下，L6肌细胞与小鼠瘦素(10(-11)-10(-8)M)孵育10分钟和1小时，葡萄糖摄取量增加15%-23%。瘦素(10(-10)-10(-9)M)最初(10分钟后)对胰岛素刺激的葡萄糖摄取抑制14-16%，但长期不起作用。瘦素刺激的葡萄糖摄取可被磷脂酰肌醇3-激酶(PI3K)抑制剂wortmannin抑制，但不能被Janus Kinase-2(JAK-2)抑制剂tyrphostin AG490抑制。这些结果表明，瘦素可以通过一个短的瘦素受体亚型直接作用于L6肌肉细胞，通过PI3K依赖的途径强烈地刺激基础(但不是胰岛素刺激的)葡萄糖摄取。
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 cells via a short leptin receptor isoform to acutely stimulate basal (but not insulin-stimulated) glucose uptake via a PI3K-dependent pathway.