Differential regulation of two glucose transporters in adipose cells from diabetic and insulin-treated diabetic rats.
Differential regulation of two glucose transporters in adipose cells from diabetic and insulin-treated diabetic rats.
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糖尿病和胰岛素治疗的糖尿病大鼠脂肪细胞中两种葡萄糖转运蛋白的差异调节。
DOI：
10.1172/jci114180
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Flier,JS
中科院分区：
文献类型：
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作者：
Kahn,BB;Charron,MJ;Lodish,HF;Cushman,SW;Flier,JS
至少有两种基因上不同的葡萄糖转运蛋白（GTs）共存于脂肪细胞中，一种克隆自人肝癌细胞和大鼠脑（HepG2/脑），另一种克隆自大鼠骨骼肌、心脏和脂肪细胞（脂肪细胞/肌肉）。在这里，我们证明了这两种GT在糖尿病和胰岛素治疗的糖尿病大鼠的脂肪细胞中的差异调节，并比较了每种GT的表达变化与胰岛素刺激的葡萄糖运输活性的显著改变。单克隆抗血清1F8免疫印迹法检测脂肪细胞/肌肉GTs （James， D. E.， R. Brown， J. Navarro， P. F. Pilch. 1988）。自然(Lond)。333:183-185)与新克隆的脂肪细胞/肌肉GT cDNA蛋白产物发生反应，糖尿病患者的水平降低87%，胰岛素治疗的水平增加到糖尿病的8.5倍。这些变化与先前通过细胞松弛素B结合和胰岛素刺激的3- o -甲基葡萄糖转运检测到的GTs在质量上一致。Northern blotting显示，脂肪/肌肉GT mRNA在糖尿病患者中减少50%，而在胰岛素治疗组中增加到6.8倍（糖尿病患者的13倍）。相比之下，抗血清检测到HepG2 GT的羧基端或人红细胞GT的GTs在糖尿病或胰岛素治疗后没有显着变化。HepG2/脑GT mRNA在糖尿病患者中没有变化，在胰岛素治疗时增加了三倍。这些结果表明：(a)脂肪细胞/肌肉GT表达的改变构成了糖尿病胰岛素特征下葡萄糖转运反应失调的分子基础，(b)大鼠脂肪细胞中两种类型GT的表达是独立调节的，(c) mRNA水平的改变只是任一种GT在体内表达调节机制的一部分。图片
At least two genetically distinct glucose transporters (GTs) coexist in adipose cells, one cloned from human hepatoma cells and rat brain (HepG2/brain) and another from rat skeletal muscle, heart, and adipose cells (adipose cell/muscle). Here we demonstrate differential regulation of these two GTs in adipose cells of diabetic and insulin-treated diabetic rats and compare changes in the expression of each GT with marked alterations in insulin-stimulated glucose transport activity. Adipose cell/muscle GTs detected by immunoblotting with the monoclonal antiserum 1F8 (James, D. E., R. Brown, J. Navarro, and P. F. Pilch. 1988. Nature (Lond.). 333:183-185), which reacts with the protein product of the newly cloned adipose cell/muscle GT cDNA, decrease 87% with diabetes and increase to 8.5-fold diabetic levels with insulin treatment. These changes concur qualitatively with previous detection of GTs by cytochalasin B binding and with insulin-stimulated 3-O-methylglucose transport. Northern blotting reveals that the adipose/muscle GT mRNA decreases 50% with diabetes and increases to 6.8-fold control (13-fold diabetic) levels with insulin treatment. In contrast, GTs detected with antisera to the carboxyl terminus of the HepG2 GT or to the human erythrocyte GT show no significant change with diabetes or insulin treatment. The HepG2/brain GT mRNA is unchanged with diabetes and increases threefold with insulin treatment. These results suggest that (a) altered expression of the adipose cell/muscle GT forms the molecular basis for the dysregulated glucose transport response to insulin characteristic of diabetes, (b) the expression of two types of GTs in rat adipose cells is regulated independently, and (c) alterations in mRNA levels are only part of the mechanism for in vivo regulation of the expression of either GT species.Images