HIGH-FAT FEEDING CAUSES INSULIN RESISTANCE AND A MARKED DECREASE IN THE EXPRESSION OF GLUCOSE TRANSPORTERS (GLUT-4) IN FAT-CELLS OF RATS
HIGH-FAT FEEDING CAUSES INSULIN RESISTANCE AND A MARKED DECREASE IN THE EXPRESSION OF GLUCOSE TRANSPORTERS (GLUT-4) IN FAT-CELLS OF RATS
复制标题
DOI：
10.1210/endo-129-2-771
复制
发表时间：
1991-08-01
期刊：
影响因子：
4.8
通讯作者：
KAHN, BB
中科院分区：
文献类型：
--
作者：
PEDERSEN, O;KAHN, CR;KAHN, BB
随着两种不同的葡萄糖转运蛋白在脂肪细胞中的鉴定，确定这些转运蛋白在与不同代谢和营养状态相关的葡萄糖转运活性改变中的作用至关重要。 在本研究中，我们评估了标准饲料（对照）、混合流质饲料和标准饲料（过度喂养）、高脂饲料、高脂饲料和高脂饲料喂养的Sprague-Dawley大鼠脂肪细胞中Glut 1和Glut 4转运蛋白的表达水平以及基础和胰岛素刺激的葡萄糖转运活性。高脂饮食与相对餐后低血糖相关低胰岛素血症（P <0.05）。 虽然高脂喂养的动物体重低于对照组大鼠（P < 0.05），但它们的身体组成显示肥胖，附睾脂肪垫增加36%（P < 0.05），脂肪细胞体积增加47%（P < 0.05）。 脂肪喂养导致每个脂肪细胞胰岛素刺激的葡萄糖转运减少78%（P < 0.05）。 与此同时，我们发现，在脂肪喂养的大鼠中，每个脂肪细胞的Glut 4蛋白和mRNA分别减少了92%和94%（P < 0.01）。 在相同的大鼠中，每个脂肪细胞的Glut 1蛋白和mRNA也显著减少（分别为62%和76%; P < 0.05）。 然而，Glut 1表达的变化与细胞骨架蛋白β-肌动蛋白的变化幅度相同，反映了在这种营养状态下几种蛋白质的表达减少。 尽管过度喂养和能量限制导致肥胖的相反变化，但葡萄糖转运速率或葡萄糖转运蛋白表达没有显着改变。 高脂喂养大鼠脂肪细胞中胰岛素刺激的葡萄糖转运受损发生在主要胰岛素反应性葡萄糖转运蛋白（Glut 4）表达显著降低的情况下。 基因表达降低可能是由慢性低胰岛素血症引起的，并可能导致在这种状态下观察到的胰岛素抵抗。
With the identification of two different glucose transporter species in adipose cells it is crucial to determine the role of these transporters in the alterations in glucose transport activity associated with different metabolic and nutritional states. In the present study we assess levels of expression of Glut 1 and Glut 4 transporters and basal and insulin-stimulated glucose transport activity in adipocytes from Sprague-Dawley rats fed standard chow (control), combined liquid diet and standard chow (overfed), high fat diet, or energy-restricted diet for 7 weeks.High fat feeding was associated with relative postprandial hypoglycemia (P < 0.05) and hypoinsulinemia (P < 0.05). Although the high fat fed animals had lower body weights (P < 0.05) than control rats, their body compositions showed obesity, with 36% heavier epididymal fat pads (P < 0.05) and a 47% increase in adipocyte volume (P < 0.05). Fat feeding caused a 78% reduction in insulin-stimulated glucose transport per adipocyte (P < 0.05). In parallel we found 92% and 94% reductions in Glut 4 protein and mRNA per adipocyte, respectively, (P < 0.01) in fat-fed rats. Substantial reductions were also seen in Glut 1 protein and mRNA per fat cell in the same rats (62% and 76%, respectively; P < 0.05). However, the changes in Glut 1 expression were of the same magnitude as changes in the cytoskeletal protein beta-actin, reflecting a decreased expression of several proteins in this nutritional state. Even though overfeeding and energy restriction brought about opposite changes in adiposity, no significant alterations were demonstrated in glucose transport rate or glucose transporter expression. The impaired insulin-stimulated glucose transport in adipose cells from high fat-fed rats occurs in the presence of a dramatic decrease in the expression of the major insulin-responsive glucose transporter (Glut 4). The reduced gene expression may be caused by chronic hypoinsulinemia and may contribute to the insulin resistance observed in this state.