ROLE OF GLUCOSE TRANSPORTERS IN GLUCOCORTICOID-INDUCED INSULIN RESISTANCE - GLUT4 ISOFORM IN RAT SKELETAL-MUSCLE IS NOT DECREASED BY DEXAMETHASONE
ROLE OF GLUCOSE TRANSPORTERS IN GLUCOCORTICOID-INDUCED INSULIN RESISTANCE - GLUT4 ISOFORM IN RAT SKELETAL-MUSCLE IS NOT DECREASED BY DEXAMETHASONE
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DOI：
10.2337/diabetes.41.6.728
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发表时间：
1992-06-01
期刊：
影响因子：
7.7
通讯作者：
WEINSTEIN, SP
中科院分区：
文献类型：
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作者：
HABER, RS;WEINSTEIN, SP
糖皮质激素过量的致糖尿病作用部分是由于外周对胰岛素的抵抗。为了验证糖皮质激素诱导的外周胰岛素抵抗可能归因于葡萄糖转运蛋白数量减少的假设，我们研究了地塞米松治疗对骨骼肌中GLUT4（胰岛素可调节的）葡萄糖转运蛋白表达的影响，骨骼肌是胰岛素介导的葡萄糖摄取的主要部位。地塞米松治疗大鼠（1 mg/天，持续1周）可诱导高血糖和高胰岛素血症。在0.1或1mg /天的剂量下，孤立比目鱼肌中胰岛素刺激的2-脱氧葡萄糖摄取减少了大于或等于50%，表明骨骼肌中存在胰岛素抵抗。深股四头肌粗膜免疫印迹显示，地塞米松处理（1 mg/d）使GLUT4蛋白量增加84%。当以单位RNA表达时，GLUT4 mRNA丰度同样增加，但当以DNA为基础表达时，由于地塞米松降低了组织RNA含量，GLUT4 mRNA丰度不变。与股四头肌相比，地塞米松处理后比目鱼肌和趾长伸肌提取物中GLUT4蛋白浓度没有显著升高。由于糖皮质激素导致表达相对较少的GLUT4蛋白的IIb型肌纤维选择性萎缩，地塞米松处理的动物四头肌中GLUT4含量的明显增加可能是由于糖皮质激素诱导的GLUT4蛋白较差的IIb型纤维的相对质量减少，导致富含GLUT4的I型和IIA型纤维的取样无意中增加。我们得出结论，糖皮质激素不会降低骨骼肌中GLUT4的含量，并且糖皮质激素诱导的骨骼肌胰岛素抵抗不是由于葡萄糖转运蛋白基因表达的抑制。
The diabetogenic effects of glucocorticoid excess are due in part to peripheral resistance to insulin. To test the hypothesis that glucocorticoid-induced peripheral insulin resistance might be attributable to a decreased number of glucose transporters, we examined the effects of dexamethasone treatment on the expression of the GLUT4 (insulin regulatable) glucose transporter in skeletal muscle, the major site of insulin-mediated glucose uptake. Dexamethasone treatment of rats (1 mg/day for 1 wk) induced hyperglycemia and hyperinsulinemia. At dosages of either 0.1 or 1 mg/day, insulin-stimulated 2-deoxyglucose uptake in isolated soleus muscle was reduced by greater-than-or-equal-to 50%, demonstrating the presence of insulin resistance in skeletal muscle. Immunoblots of crude membranes from deep quadriceps muscle showed that dexamethasone treatment (1 mg/day) increased the amount of GLUT4 protein by 84%. GLUT4 mRNA abundance was similarly increased when expressed per unit RNA but was unchanged when expressed on a DNA basis because the tissue RNA content was decreased by dexamethasone. In contrast to quadriceps, GLUT4 protein concentration in soleus and extensor digitorum longus extracts was not significantly increased by dexamethasone treatment. Because glucocorticoids cause selective atrophy of type IIb muscle fibers, which express relatively less GLUT4 protein, the apparent increase in GLUT4 content in quadriceps muscle from dexamethasone-treated animals may have resulted from inadvertent increased sampling of GLUT4-enriched type I and IIA fibers, caused by a glucocorticoid-induced decrease in the relative mass of the GLUT4-poor type IIb fibers. We conclude that glucocorticoids do not decrease GLUT4 content in skeletal muscle and that glucocorticoid-induced insulin resistance in this tissue is not due to suppression of glucose transporter gene expression.