Lin J L, Asano T, Shibasaki Y, Tsukuda K, Katagiri H, Ishihara H, Takaku F, Oka Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Diabetologia. 1991 Jul;34(7):477-82. doi: 10.1007/BF00403283.
To elucidate the cellular mechanisms of glucose intolerance associated with aging, both the protein and mRNA levels of glucose transporter isoforms were studied in the various tissues of young (7-week-old) and aged (20-month-old) rats. GluT4 (adipose/muscle-type glucose transporter) protein, which is specifically expressed in insulin-responsive tissues, was selectively decreased per milligram of cellular membrane protein in both the epididymal fat tissues and the gastrocnemius muscle of the aged rats compared with the young rats. When the changes in total cellular membranes per gram of tissue are taken into account, a further decrease in GluT4 protein per gram of tissue was observed in the tissues of the aged rats compared with the young rats. The decreased amount of GluT4 protein in the fat tissues of the aged rats is probably due to the decreased protein synthesis rather than the stability, since GluT4 mRNA/micrograms of cellular total RNA was also decreased. In contrast, GluT4 mRNA in the gastrocnemius muscle was rather increased and a ratio of GluT4 protein/GluT4 mRNA was decreased by 70% in the aged rats, suggesting that the translational efficiency and/or stability of GluT4 protein is decreased in the skeletal muscle of the aged rats compared with the young rats. GluT2 (liver-type glucose transporter) protein and mRNA in the liver were also decreased in the aged rats, while no apparent decrease in GluT1 (HepG2/brain-type glucose transporter) protein/mg of cellular membrane protein was observed in the skeletal muscle and fat tissues of the aged rats compared with the young rats.(ABSTRACT TRUNCATED AT 250 WORDS)
为阐明与衰老相关的葡萄糖不耐受的细胞机制,研究了年轻(7周龄)和老年(20月龄)大鼠各组织中葡萄糖转运异构体的蛋白质和mRNA水平。与年轻大鼠相比,老年大鼠附睾脂肪组织和腓肠肌中每毫克细胞膜蛋白中胰岛素反应性组织中特异性表达的葡萄糖转运蛋白4(脂肪/肌肉型葡萄糖转运蛋白)选择性降低。当考虑每克组织中总细胞膜的变化时,与年轻大鼠相比,老年大鼠组织中每克组织的葡萄糖转运蛋白4进一步降低。老年大鼠脂肪组织中葡萄糖转运蛋白4的减少可能是由于蛋白质合成减少而非稳定性降低,因为每微克细胞总RNA中的葡萄糖转运蛋白4 mRNA也减少了。相反老年大鼠腓肠肌中葡萄糖转运蛋白4 mRNA反而增加,且葡萄糖转运蛋白4蛋白与葡萄糖转运蛋白4 mRNA的比值降低了70%,这表明与年轻大鼠相比,老年大鼠骨骼肌中葡萄糖转运蛋白4的翻译效率和/或稳定性降低。老年大鼠肝脏中葡萄糖转运蛋白2(肝型葡萄糖转运蛋白)蛋白和mRNA也减少,但与年轻大鼠相比,老年大鼠骨骼肌和脂肪组织中每毫克细胞膜蛋白的葡萄糖转运蛋白1(HepG2/脑型葡萄糖转运蛋白)未明显降低。(摘要截短于250字)