Wuarin L, Guertin D M, Ishii D N
Department of Physiology, Colorado State University, Fort Collins 80523.
Exp Neurol. 1994 Nov;130(1):106-14. doi: 10.1006/exnr.1994.1189.
Diabetic neuropathy is a common and disabling complication of diabetes mellitus whose pathogenesis remains unknown. Insulin-like growth factors (IGFs) have been recently implicated in the development and maintenance of the peripheral nervous system, and circulating IGF levels are decreased in experimental and clinical diabetes. Therefore, we tested the hypothesis that IGF gene expression is reduced in peripheral nerves early after the onset of diabetes. Sciatic nerves from nondiabetic and streptozotocin-treated rats were removed 5-7 days after the induction of diabetes. RNA was isolated and analyzed by Northern and slot blots. IGF-I mRNA content was significantly decreased per milligram wet weight nerve (P < 0.025) as well as per poly(A)+ RNA (P < 0.01) in diabetic vs nondiabetic nerves. Likewise, the amount of IGF-II mRNA was significantly decreased per milligram wet weight nerve (P < 0.01) as well as per poly(A)+ RNA (P < 0.005). These effects were selective because histone 3.3 mRNA content, as well as poly(A)+ mRNA content, per milligram nerve were unchanged. Insulin treatment partially prevented this decline in IGF-I and IGF-II mRNA levels. The diminished IGF mRNA content is one of the earliest biochemical abnormalities to be observed in the diabetic nerve, supporting the hypothesis that a reduction in IGF activity in diabetic nerves precedes and contributes to the development of neuropathy.
糖尿病性神经病变是糖尿病常见且致残的并发症，其发病机制尚不清楚。胰岛素样生长因子（IGFs）最近被认为与外周神经系统的发育和维持有关，并且在实验性和临床糖尿病中循环IGF水平降低。因此，我们检验了糖尿病发病后早期外周神经中IGF基因表达降低的假说。在糖尿病诱导后5 - 7天，取出非糖尿病大鼠和经链脲佐菌素处理大鼠的坐骨神经。分离RNA并通过Northern印迹和狭缝印迹进行分析。与非糖尿病神经相比，糖尿病神经中每毫克湿重神经的IGF - I mRNA含量显著降低（P < 0.025），每多聚腺苷酸（poly(A)+）RNA中的含量也显著降低（P < 0.01）。同样，每毫克湿重神经的IGF - II mRNA量显著降低（P < 0.01），每多聚腺苷酸（poly(A)+）RNA中的含量也显著降低（P < 0.005）。这些影响具有选择性，因为每毫克神经中的组蛋白3.3 mRNA含量以及多聚腺苷酸（poly(A)+）mRNA含量没有变化。胰岛素治疗部分阻止了IGF - I和IGF - II mRNA水平的这种下降。IGF mRNA含量的减少是在糖尿病神经中最早观察到的生化异常之一，支持了糖尿病神经中IGF活性降低先于并促成神经病变发展的假说。
