Wuarin L, Namdev R, Burns J G, Fei Z J, Ishii D N
Department of Physiology, Colorado State University, Fort Collins 805231, USA.
J Neurochem. 1996 Aug;67(2):742-51. doi: 10.1046/j.1471-4159.1996.67020742.x.
Diabetic encephalopathy, characterized by structural, electrophysiological, neurochemical, and cognitive abnormalities, is observed in insulin-dependent diabetes mellitus (IDDM) and non-IDDM (NIDDM). Identification of early biochemical lesions potentially may provide clues pointing to its pathogenesis. Insulin-like growth factors (IGFs) are neurotrophic factors that recently have been implicated in the pathogenesis of diabetic neuropathy. Because IGF-II is the predominant IGF in adult brain, we tested the hypothesis that IGF-II gene expression is decreased in the CNS in both IDDM and NIDDM. Brain and spinal cord were isolated from streptozotocin-diabetic rats, a model of IDDM with weight loss and impaired insulin production. IGF-II mRNA content was measured by northern and slot blots. After 2 weeks of diabetes, IGF-II mRNA content per milligram of tissue wet weight, as well as per unit of poly(A)+ RNA, declined significantly (p < or = 0.05) in brain and spinal cord. Insulin replacement therapy partially restored IGF-II mRNA levels in brain, cortex, medulla, and spinal cord. The obese, hyperinsulinemic, and spontaneously diabetic (fa/fa) Zucker rat was used as a model of NIDDM. Brain weight (p < 0.025) and IGF-II mRNA contents (p < 0.01) were significantly decreased in (fa/fa) versus lean nondiabetic (+ /?) rats. Therefore, the decline in IGF-II mRNA levels in diabetic brain was independent of the type of diabetes, the direction of change in body weight, and the insulinemic state. We speculate that this early biochemical lesion may contribute to the development of diabetic encephalopathy.
糖尿病性脑病以结构、电生理、神经化学和认知异常为特征，在胰岛素依赖型糖尿病（IDDM）和非胰岛素依赖型糖尿病（NIDDM）中均可观察到。识别早期生化损伤可能为其发病机制提供线索。胰岛素样生长因子（IGFs）是神经营养因子，最近被认为与糖尿病性神经病变的发病机制有关。由于IGF-II是成年大脑中主要的IGF，我们检验了这样一个假设，即IDDM和NIDDM患者中枢神经系统中IGF-II基因表达均降低。从链脲佐菌素诱导的糖尿病大鼠中分离出脑和脊髓，链脲佐菌素诱导的糖尿病大鼠是一种伴有体重减轻和胰岛素分泌受损的IDDM模型。通过Northern印迹法和狭缝印迹法测量IGF-II mRNA含量。糖尿病2周后，脑和脊髓中每毫克组织湿重以及每单位聚腺苷酸（A）+RNA中的IGF-II mRNA含量均显著下降（p≤0.05）。胰岛素替代疗法部分恢复了脑、皮质、髓质和脊髓中的IGF-II mRNA水平。肥胖、高胰岛素血症且自发糖尿病的（fa/fa）Zucker大鼠被用作NIDDM模型。与瘦的非糖尿病（+/？）大鼠相比，（fa/fa）大鼠的脑重量（p<0.025）和IGF-II mRNA含量（p<0.01）显著降低。因此，糖尿病脑中IGF-II mRNA水平的下降与糖尿病类型、体重变化方向和胰岛素血症状态无关。我们推测这种早期生化损伤可能促成糖尿病性脑病的发展。
