Coordinate regulation of glucose transporter function, number, and gene expression by insulin and sulfonylureas in L6 rat skeletal muscle cells.
Coordinate regulation of glucose transporter function, number, and gene expression by insulin and sulfonylureas in L6 rat skeletal muscle cells.
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L6 大鼠骨骼肌细胞中胰岛素和磺酰脲类药物对葡萄糖转运蛋白功能、数量和基因表达的协调调节。
DOI：
10.1172/jci114170
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Smith,RJ
中科院分区：
文献类型：
--
作者：
Wang,PH;Moller,D;Flier,JS;Nayak,RC;Smith,RJ
用培养的大鼠骨骼肌细胞L 6系研究了磺脲类药物对葡萄糖转运系统的胰外作用。胰岛素（10（-7）M）在孵育8小时后使分化的L 6肌管中的2-脱氧葡萄糖摄取增加30-40%。磺酰脲类药物妥拉磺酰胺（0.6 mg/ml，22 h）在不存在胰岛素的情况下对葡萄糖摄取没有影响，但可使胰岛素刺激的2-脱氧葡萄糖摄取增加两倍。葡萄糖转运蛋白的总细胞含量通过固相ELISA方法用单克隆抗转运蛋白抗体进行评估。胰岛素（8 h）增加葡萄糖转运蛋白的数量，在10（-7）M时最大增加两倍，剂量-反应曲线与胰岛素刺激葡萄糖摄取的曲线相似。尽管缺乏对葡萄糖摄取的影响，但单独使用甲磺磺酰胺（0.6 mg/ml）可使转运蛋白的细胞含量增加70%。以Hep G2葡萄糖转运蛋白cDNA为探针，研究胰岛素和妥拉磺脲对转运蛋白基因表达的影响。胰岛素使转运蛋白mRNA水平增加1.7倍，妥拉磺脲使其增加1.5倍，胰岛素和妥拉磺脲联合使转运蛋白mRNA增加3倍。它的结论是，磺酰脲类药物，连同胰岛素，增强葡萄糖摄取L 6骨骼肌细胞的功能葡萄糖转运分子的数量增加。胰岛素和磺酰脲类药物在体内对骨骼肌葡萄糖转运系统的长期调节可能涉及转运蛋白功能、数量和基因表达的类似变化。图片
The extrapancreatic actions of sulfonylureas on the glucose transport system were studied in the L6 line of cultured rat skeletal muscle cells. Insulin (10(-7) M) increased 2-deoxyglucose uptake in differentiated L6 myotubes by 30-40% after 8 h of incubation. The sulfonylurea tolazamide (0.6 mg/ml, 22 h) had no effect on glucose uptake in the absence of insulin, but increased insulin-stimulated 2-deoxyglucose uptake twofold. The total cellular content of glucose transporters was assessed with a monoclonal anti-transporter antibody by a solid-phase ELISA method. Insulin (8 h) increased the quantity of glucose transporters, with a maximal twofold increase at 10(-7) M and a dose-response curve similar to that for insulin stimulation of glucose uptake. In spite of its lack of effect on glucose uptake, tolazamide alone (0.6 mg/ml) increased the cellular content of transporters by 70%. The effects of insulin and tolazamide on transporter gene expression were studied with probes derived from Hep G2 glucose transporter cDNA. Insulin increased the transporter mRNA level 1.7-fold, tolazamide increased it 1.5-fold, and the combination of insulin and tolazamide increased transporter mRNA 3-fold. It is concluded that sulfonylureas, together with insulin, enhance glucose uptake in L6 skeletal muscle cells by increasing the number of functioning glucose transport molecules. The long-term regulation of the glucose transport system in skeletal muscle by insulin and sulfonylureas in vivo may involve similar changes in transporter function, number, and gene expression.Images