Peavy D E, Taylor J M, Jefferson L S
Proc Natl Acad Sci U S A. 1978 Dec;75(12):5879-83. doi: 10.1073/pnas.75.12.5879.
We have studied the effects of alloxan-induced diabetes and subsequent insulin replacement on albumin and total hepatic protein synthesis. Diabetes resulted in a reduction to approximately 20% of normal in albumin synthesis relative to the rate of total protein synthesis in vivo and a reduction to 10% in the absolute rate of albumin secretion by perfused livers. In contrast, the synthesis of total secretory protein and retained hepatic protein was affected to a lesser extent by diabetes. Treatment of diabetic rats with insulin restored rates of albumin and total hepatic protein synthesis to normal levels. The molecular basis of these alterations in albumin synthesis was investigated by examining albumin mRNA levels in livers of normal, diabetic, and insulin-treated diabetic animals. The level of albumin mRNA, whether assayed by cell-free translation or by hybridization to a specific complementary DNA probe, was markedly decreased in livers of diabetic animals and was restored to normal by insulin treatment. These changes occurred in parallel with changes in the rates of albumin secretion observed in perfused liver, suggesting that albumin mRNA content is the primary factor responsible for altering rates of albumin synthesis under these conditions.
我们研究了四氧嘧啶诱导的糖尿病及随后胰岛素替代治疗对白蛋白和肝脏总蛋白合成的影响。糖尿病导致体内白蛋白合成相对于总蛋白合成速率降低至正常水平的约20%，灌注肝脏白蛋白分泌的绝对速率降低至10%。相比之下，糖尿病对总分泌蛋白和肝脏留存蛋白合成的影响较小。用胰岛素治疗糖尿病大鼠可使白蛋白和肝脏总蛋白合成速率恢复至正常水平。通过检测正常、糖尿病及胰岛素治疗的糖尿病动物肝脏中白蛋白mRNA水平，研究了白蛋白合成这些改变的分子基础。无论是通过无细胞翻译检测还是通过与特异性互补DNA探针杂交检测，糖尿病动物肝脏中白蛋白mRNA水平均显著降低，而胰岛素治疗可使其恢复正常。这些变化与灌注肝脏中观察到的白蛋白分泌速率变化平行，表明在这些条件下，白蛋白mRNA含量是改变白蛋白合成速率的主要因素。
