Low birthweight is associated with specific changes in muscle insulin-signalling protein expression
Low birthweight is associated with specific changes in muscle insulin-signalling protein expression
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DOI：
10.1007/s00125-005-1669-7
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发表时间：
2005-03-01
期刊：
影响因子：
8.2
通讯作者：
Vaag, AA
中科院分区：
文献类型：
--
作者：
Ozanne, SE;Jensen, CB;Vaag, AA
目的/假设：低出生体重的人在成年后患2型糖尿病的风险增加。这种现象的机械基础尚不清楚。在这里，我们研究了早期生长限制对人类队列和大鼠模型骨骼肌中胰岛素信号蛋白表达的影响。研究方法：我们招募了20名低出生体重的年轻男性（平均出生体重2702 ± 202 g）和20名年龄匹配的对照组（平均出生体重3801 ± 99 g）。从股外侧肌获得活组织检查，并确定所选胰岛素信号蛋白的蛋白表达。用于本研究的大鼠是妊娠期和哺乳期饲喂标准（20%）蛋白质饲料或低（8%）蛋白质饲料的母鼠所生的雄性后代。在成年后代的比目鱼肌中测定蛋白质表达。结果：低出生体重受试者显示蛋白激酶C（PKC）zeta，p85 α，p110 β和GLUT 4的肌肉表达减少。PKC zeta，GLUT 4和p85也在低蛋白饮食大鼠的肌肉中减少。与对照组相比，低出生体重的人和喂食低蛋白饮食的大鼠中研究的其他蛋白质没有变化。结论/解释：我们发现与对照组相比，低出生体重受试者中特异性胰岛素信号蛋白的表达降低。这些变化先于糖耐量受损的发生。低出生体重的男性与喂食低蛋白饮食的大鼠的后代的蛋白质表达谱的相似性表明啮齿动物模型是人类情况的准确代表。它还提供了一个潜在的机制解释，为什么胎儿环境在确定发展2型糖尿病的风险中起着重要作用。
Aims/hypothesis: People with low birthweight have an increased risk of developing type 2 diabetes mellitus in adulthood. The mechanistic basis of this phenomenon is not known. Here we investigate the effect of early growth restriction on the expression of insulin-signalling proteins in skeletal muscle in a human cohort and a rat model. Methods: We recruited 20 young men with low birthweight (mean birthweight 2702 +/- 202 g) and 20 age-matched control subjects (mean birthweight 3801 +/- 99 g). Biopsies were obtained from the vastus lateralis muscle and protein expression of selected insulin-signalling proteins was determined. Rats used for this study were male offspring born to dams fed a standard (20%) protein diet or a low (8%) protein diet during pregnancy and lactation. Protein expression was determined in soleus muscle from adult offspring. Results: Low-birthweight subjects showed reduced muscle expression of protein kinase C (PKC)zeta, p85 alpha, p110 beta and GLUT4. PKC zeta, GLUT4 and p85 were also reduced in the muscle of rats fed a low-protein diet. Other proteins studied were unchanged in low-birthweight humans and in rats fed a low-protein diet when compared with control groups. Conclusions/interpretation: We found decreased expression of specific insulin-signalling proteins in low-birthweight subjects compared to controls. These changes precede the onset of impaired glucose tolerance. The similarity of protein expression profile in the men with low birthweight compared to that of the offspring of rats fed a low-protein diet suggests that the rodent model is an accurate representation of the human situation. It also provides a potential mechanistic explanation as to why the fetal environment plays an important role in determining risk of developing type 2 diabetes.