大鼠追赶生长早期脂肪组织和骨骼肌葡萄糖代谢差异及其机制

Differences of glucose metabofism between adipose tissue and skeletal muscle in the early stage of catch-up growth in rats and its mechanism

目的观察追赶生长过程中脂肪组织和骨骼肌葡萄糖利用状况，初步探讨脂肪组织追赶生长的发生机制。方法将雄性Wistar大鼠随机分为正常对照组（NC）和追赶生长组（RN）。通过限制饮食（NC组食量的50％）4周后给予自由开放普通饮食建立追赶生长大鼠模型，分别于实验的第5周末（NC1组和RN1组）、第6周末（NC2组和RN2组）进行检测。运用[^3H]-脱氧葡萄糖测定骨骼肌、脂肪组织葡萄糖摄取率，RT—PCR、Western印迹法检测葡萄糖转运子4（Glut4）的mRNA及膜蛋白水平。结果与NC1组相比，RN1组大鼠脂肪组织葡萄糖摄取率升高了189．6％（P〈0.01），而骨骼肌组织则下降了36．5％（P〈0．05）；开放饮食2周后，RN2组大鼠脂肪组织葡萄糖摄取率较NC2组增加了157．3％（P〈0．01），骨骼肌组织则减少了41．5％（P〈0．05）。而RN与NC各组间骨骼肌和脂肪组织Glut4的mRNA表达水平的差异均无统计学意义。但RN1组和RN2组胰岛素刺激后骨骼肌细胞膜上Glut4蛋白水平分别较相应的NC1组和NC2组下降了46．5％（P〈0．01）和32．1％（P〈0．05）；脂肪组织则分别升高了116．5％和89．9％（均P〈0，01）。结论追赶生长的早期即出现了葡萄糖由骨骼肌向脂肪组织的转移，导致脂肪组织快速追赶生长。胰岛素刺激的Glut4向细胞膜的转位发生组织特异性改变可能是导致这一变化的机制之一。

Objective To observe the glucose utilization in adipose tissue and skeletal muscle during catch-up growth, and to explore the mechanism of catch-up growth of adipose tissue. Methods Male Wistar rats were randomly divide into normal control group （NC） and catch-up group （RN）. Rats in RN group received 50% of food consumed by NC group for 4 weeks, then were re-fed spontaneously as the rats in NC group. In the end of the fifth week （NC1 group and RN1 group） and the sixth week（NC2 group and RN2 group）, the experiment was performed. [ ^3H]-2-deoxy-glucose was used for detecting the glucose uptake rate. RT-PCR and Western-blot were used for detecting the levels of mRNA and membrane protein of glucose transporter-4 （ Glut4 ）. Results The glucose uptake rates in adipose tissue and skeletal muscle of RN1 group increased by 189.6% （P 〈 0. 01 ） and reduced by 36.5% （P 〈 0.05 ） respectively, as compared with NC1 group. After 2 weeks of catch-up growth, the glucose uptake rates in adipose tissue of RN2 group increased by 157.3% （ P 〈 0.01 ） and decreased by 41.5% （ P 〈0.05 ） in skeletal muscle as compared with NC2 group. However, no significant difference in Glut4 mRNA levels in muscle or in adipose tissue between NC and RN groups were found . The membrane protein of Glut4 after insulin-stimulating in RN 1 group and RN2 group reduced by about 46.5 % （ P 〈 0.01 ） and 32.1% （ P 〈 0.05 ） in muscle and increased by 116.5% （P 〈0.01 ）and 89.9% （P 〈0.01 ） in adipose tissue respectively. Conclusion There exists the redistribution of glucose from skeletal muscle to adipose tissue during the early stage of catch-up growth, which results in the catch-up growth of adipose tissue. This change is induced by the tissue-specific alteration of insulin-stimulated Glut4 protein translocation.