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瘦素在体外对大鼠骨骼肌基础葡萄糖代谢和胰岛素刺激的葡萄糖代谢无影响。

Failure of leptin to affect basal and insulin-stimulated glucose metabolism of rat skeletal muscle in vitro.

作者信息

Fürnsinn C, Brunmair B, Furtmüller R, Roden M, Englisch R, Waldhäusl W

机构信息

Department of Medicine III, University of Vienna, Austria.

出版信息

Diabetologia. 1998 May;41(5):524-9. doi: 10.1007/s001250050941.

DOI:10.1007/s001250050941
PMID:9628268
Abstract

Studies on different isolated tissues have provided evidence that leptin may directly modulate cellular glucose handling. The present study was performed to elucidate leptin's action on basal and insulin-stimulated glucose metabolism in native muscle tissue, which under physiological circumstances is the quantitatively most important target tissue of insulin. Isolated rat soleus muscle strips were incubated for 1 h in the absence or presence of leptin (0, 1, 10, or 100 nmol/l) under basal or insulin-stimulated conditions (10 nmol/l). No effects of leptin were found on the rates of 3H-2-deoxy-glucose transport (basal: control, 314+/-14; 1 nmol/l leptin, 320+/-17; 10 nmol/l leptin, 314+/-13; 100 nmol/l leptin, 322+/-16; insulin-stimulated: control, 690+/-33; 1 nmol/l leptin, 691+/-29; 10 nmol/l leptin, 665+/-26; 100 nmol/l leptin, 664+/-27; cpm x mg(-1) x h(-1); NS vs respective control) and on net glucose incorporation into glycogen (basal: control, 1.75+/-0.18; 1 nmol/l leptin, 2.01+/-0.13; 10 nmol/l leptin, 1.92+/-0.11; 100 nmol/l leptin, 1.81+/-0.13; insulin-stimulated: control, 5.98+/-0.40; 1 nmol/l leptin, 5.93+/-0.30; 10 nmol/l leptin, 5.46+/-0.25; 100 nmol/l leptin, 5.85+/-0.30; micromol x g(-1) x h(-1); NS vs respective control). In parallel, leptin failed to affect rates of aerobic and anaerobic glycolysis as well as muscle glycogen content. Further experiments revealed that the inability of leptin to directly affect muscle glucose handling prevailed independently of muscle fiber type (soleus and epitrochlearis muscle), of ambient insulin concentrations (0-30 nmol/l), and of leptin exposure time (1 h or 6 h). Thus, our findings fail to support speculations about a physiological role of direct insulin-mimetic or insulin-desensitizing effects of leptin on skeletal muscle tissue.

摘要

对不同分离组织的研究已提供证据表明,瘦素可能直接调节细胞对葡萄糖的处理。本研究旨在阐明瘦素对天然肌肉组织中基础状态及胰岛素刺激下葡萄糖代谢的作用,在生理情况下,天然肌肉组织是胰岛素在数量上最重要的靶组织。将分离的大鼠比目鱼肌条在基础状态或胰岛素刺激状态(10 nmol/l)下,于不存在或存在瘦素(0、1、1、10或100 nmol/l)的情况下孵育1小时。未发现瘦素对3H-2-脱氧葡萄糖转运速率有影响(基础状态:对照组,314±14;1 nmol/l瘦素组,320±17;10 nmol/l瘦素组,314±13;100 nmol/l瘦素组,322±16;胰岛素刺激状态:对照组,690±33;1 nmol/l瘦素组,691±29;10 nmol/l瘦素组,665±26;100 nmol/l瘦素组,664±27;cpm×mg⁻¹×h⁻¹;与各自对照组相比无显著差异),也未发现对葡萄糖净合成糖原的速率有影响(基础状态:对照组,1.75±0.18;1 nmol/l瘦素组,2.01±0.13;10 nmol/l瘦素组,1.92±0.11;100 nmol/l瘦素组,1.81±0.13;胰岛素刺激状态:对照组,5.98±0.40;1 nmol/l瘦素组,5.93±0.30;10 nmol/l瘦素组,5.46±0.25;100 nmol/l瘦素组,5.85±0.30;μmol×g⁻¹×h⁻¹;与各自对照组相比无显著差异)。同时,瘦素未能影响有氧和无氧糖酵解速率以及肌肉糖原含量。进一步实验表明,瘦素无法直接影响肌肉对葡萄糖的处理,这一现象不受肌肉纤维类型(比目鱼肌和肱三头肌)、环境胰岛素浓度(0 - 30 nmol/l)以及瘦素暴露时间(1小时或6小时)的影响。因此,我们的研究结果不支持关于瘦素对骨骼肌组织具有直接模拟胰岛素或使胰岛素脱敏的生理作用的推测。

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Leptin reduces the expression and increases the phosphorylation of the negative regulators of GLUT4 traffic TBC1D1 and TBC1D4 in muscle of ob/ob mice.瘦素可降低 ob/ob 小鼠肌肉中 GLUT4 转运的负调节因子 TBC1D1 和 TBC1D4 的表达,并增加其磷酸化。
PLoS One. 2012;7(1):e29389. doi: 10.1371/journal.pone.0029389. Epub 2012 Jan 9.