Schäfer M, Erdö S L
Department of Anatomy, Georg-August University, Göttingen, FRG.
Brain Res. 1992 May 15;580(1-2):331-3. doi: 10.1016/0006-8993(92)90962-9.
The effect of insulin on the sensitivity of neurons to excitatory amino acid-induced cytotoxic cell death was examined in primary cultures of the rat cerebral cortex. Cells developed for two weeks in serum supplemented medium in the presence or absence of insulin, insulin-like growth factor or b-fibroblast growth factor. Excitotoxic cell death was induced by 1 mmol/l glutamate, N-methyl-D-aspartate, kainate or quisqualate. The vulnerability of cells was evaluated by the measurement of lactate dehydrogenase release due to cytotoxic injury. In contrast to the moderate evaluation of protein content by all the 3 growth factors, only insulin increased the vulnerability of cells to the neurotoxic effects of glutamate and of the 3 excitatory amino acid receptor agonists examined. Our results show that the induction of vulnerability in cortical cultures is a specific action of insulin and not a general effect of growth factors. Moreover, the increased vulnerability to N-methyl-D-aspartate, quisqualate and kainate suggests that the effect of insulin is exerted through intracellular mechanisms other than a selective induction of one subpopulation of excitatory amino acid receptors.
在大鼠大脑皮层原代培养物中研究了胰岛素对神经元对兴奋性氨基酸诱导的细胞毒性细胞死亡敏感性的影响。细胞在补充血清的培养基中培养两周，培养基中存在或不存在胰岛素、胰岛素样生长因子或β-成纤维细胞生长因子。通过1 mmol/L谷氨酸、N-甲基-D-天冬氨酸、海人酸或喹啉酸诱导兴奋性毒性细胞死亡。通过测量细胞毒性损伤导致的乳酸脱氢酶释放来评估细胞的易损性。与所有3种生长因子对蛋白质含量的适度评估相反，只有胰岛素增加了细胞对谷氨酸和所检测的3种兴奋性氨基酸受体激动剂神经毒性作用的易损性。我们的结果表明，皮层培养物中易损性的诱导是胰岛素的特异性作用，而非生长因子的普遍作用。此外，对N-甲基-D-天冬氨酸、喹啉酸和海人酸易损性的增加表明，胰岛素的作用是通过细胞内机制发挥的，而非通过选择性诱导某一亚群兴奋性氨基酸受体。
