INSULIN DOWN-REGULATES EXPRESSION OF THE INSULIN-RESPONSIVE GLUCOSE TRANSPORTER (GLUT4) GENE - EFFECTS ON TRANSCRIPTION AND MESSENGER-RNA TURNOVER
INSULIN DOWN-REGULATES EXPRESSION OF THE INSULIN-RESPONSIVE GLUCOSE TRANSPORTER (GLUT4) GENE - EFFECTS ON TRANSCRIPTION AND MESSENGER-RNA TURNOVER
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DOI：
10.1073/pnas.90.2.512
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发表时间：
1993-01-15
影响因子：
11.1
通讯作者：
LANE, MD
中科院分区：
文献类型：
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作者：
FLORESRIVEROS, JR;MCLENITHAN, JC;LANE, MD
胰岛素快速抑制3T3-L1小鼠脂肪细胞中编码胰岛素反应性葡萄糖转运体(GLUT4)基因的表达。一旦接触到激素，GLUT4mRNA的细胞水平(T1/2几乎相当于2.5小时)在10小时内下降到最初水平的20-30%。紧随其后的是GLUT4蛋白水平的类似下降。GLUT4基因转录的快速抑制和GLUT4消息周转率的增加都是GLUT4mRNA下调的结果。由于长期暴露在胰岛素中，3T3-L1脂肪细胞失去了胰岛素急性刺激己糖摄取的能力。这些发现解释了在非胰岛素依赖型(2型)糖尿病中观察到的脂肪组织中葡萄糖摄取对胰岛素的抵抗，特别是与高胰岛素血症和肥胖症相关的糖尿病。
Insulin rapidly represses expression of the gene encoding the insulin-responsive glucose transporter (GLUT4) in 3T3-L1 mouse adipocytes. Upon exposure to the hormone the cellular level of GLUT4 mRNA falls (t1/2 almost-equal-to 2.5 hr) to 20-30% of its initial level within 10 hr. This is followed by a similar decrease in the level of GLUT4 protein. Down-regulation of GLUT4 mRNA is a result of both rapid repression of transcription of the GLUT4 gene and an increased rate of turnover of the GLUT4 message. As a consequence of prolonged exposure to insulin, 3T3-L1 adipocytes lose their capacity for acute stimulation of hexose uptake by insulin. These findings provide an explanation for the resistance of glucose uptake to insulin in adipose tissue observed in non-insulin-dependent (type 2) diabetes mellitus, particularly that associated with hyperinsulinemia and obesity.