Insulin resistance selectively alters cell-surface glucose transporters but not their total protein expression in equine skeletal muscle.
Insulin resistance selectively alters cell-surface glucose transporters but not their total protein expression in equine skeletal muscle.
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DOI：
10.1111/j.1939-1676.2010.0674.x
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发表时间：
2011-03
影响因子：
2.6
通讯作者：
A. Waller;T. Burns;M. Mudge;J. Belknap;V. Lacombe
中科院分区：
文献类型：
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作者：
A. Waller;T. Burns;M. Mudge;J. Belknap;V. Lacombe
背景胰岛素抵抗（IR）在人类中已被广泛认识，最近在马中也被广泛认识，但其潜在机制仍不清楚。葡萄糖转运蛋白4（GLUT 4）转运至细胞表面是胰岛素敏感组织中葡萄糖摄取的限制步骤。虽然调控GLUT易位的下游信号通路还没有很好的定义，但AS 160最近已成为一个潜在的关键组分。此外，GLUT 12（最近发现的胰岛素敏感性GLUT之一）在IR期间的作用尚不清楚。假设/假设我们假设在患有IR动物胰岛素敏感（IS）或IR痉挛的马中，细胞表面GLUT将通过AS 160依赖性途径在肌肉中减少（n = 5/组）。方法根据胰岛素改良的频繁采样IV葡萄糖耐量试验结果，对IS或IR患者进行肌肉活检。通过外表面双甘露糖光标记方法，我们具体定量了活性细胞表面GLUT 4和GLUT 12转运蛋白。通过蛋白质印迹法测定总GLUT 4和GLUT 12以及AS 160蛋白表达。结果IR通过AS 160非依赖性途径降低基底细胞表面GLUT 4表达（P= 0.027），但不影响GLUT 12，而不影响总GLUT 4和GLUT 12含量。细胞表面GLUT 4在两组中均未被胰岛素刺激进一步增强。结论和临床重要性IR通过降低细胞表面GLUT 4活性诱导骨骼肌葡萄糖转运途径缺陷。
BACKGROUND Insulin resistance (IR) has been widely recognized in humans, and more recently in horses, but its underlying mechanisms are still not well understood. The translocation of glucose transporter 4 (GLUT4) to the cell surface is the limiting step for glucose uptake in insulin-sensitive tissues. Although the downstream signaling pathways regulating GLUT translocation are not well defined, AS160 recently has emerged as a potential key component. In addition, the role of GLUT12, one of the most recently identified insulin-sensitive GLUTs, during IR is unknown. HYPOTHESIS/OBJECTIVES We hypothesized that cell-surface GLUT will be decreased in muscle by an AS160-dependent pathway in horses with IR. ANIMALS Insulin-sensitive (IS) or IR mares (n = 5/group). METHODS Muscle biopsies were performed in mares classified as IS or IR based on results of an insulin-modified frequently sampled IV glucose tolerance test. By an exofacial bis-mannose photolabeled method, we specifically quantified active cell-surface GLUT4 and GLUT12 transporters. Total GLUT4 and GLUT12 and AS160 protein expression were measured by Western blots. RESULTS IR decreased basal cell-surface GLUT4 expression (P= .027), but not GLUT12, by an AS160-independent pathway, without affecting total GLUT4 and GLUT12 content. Cell-surface GLUT4 was not further enhanced by insulin stimulation in either group. CONCLUSIONS AND CLINICAL IMPORTANCE IR induced defects in the skeletal muscle glucose transport pathway by decreasing active cell-surface GLUT4.