Sonnewald U, Wang A Y, Schousboe A, Erikson R, Skottner A
MR-Center, SINTEF UNIMED, Trondheim, Norway.
Dev Neurosci. 1996;18(5-6):443-8. doi: 10.1159/000111439.
Using 13C nuclear magnetic resonance spectroscopy in combination with conventional biochemical techniques, effects of insulin and IGF-I on energy metabolism and cell viability were studied in cerebral cortical neurons, astrocytes and cocultures thereof during normoxia and hypoxia. Lactate dehydrogenase leakage was used to monitor the cytoprotective effects of IGF-I and insulin. Thus, during normoxia both peptides decreased LDH leakage from neurons. During hypoxia, however, this protection was only observed when insulin was present. Interestingly, neurons showed much less LDH leakage during hypoxia than astrocytes or cocultures. A possible explanation could be an increased glycolysis in neurons. Thus, lactate production and glucose consumption were increased severalfold in neurons during hypoxia whereas astrocytes and cocultures only showed a slight increase. Both insulin and IGF-I increased glucose metabolism during normoxia in astrocytes but not in neurons, whereas during hypoxia this increase was less pronounced. Using [1-13C]glucose it could be demonstrated that production of lactate from mitochondrial precursors was, in the presence of insulin or IGF-I, down regulated in astrocytes but increased in neurons during normoxia. This route for lactate production was not used during hypoxia and incorporation into the C-3 position of lactate approached the theoretical maximum of 50%.
运用碳-13核磁共振波谱技术并结合传统生化技术，在常氧和缺氧条件下，研究了胰岛素和胰岛素样生长因子-I（IGF-I）对大脑皮质神经元、星形胶质细胞及其共培养物能量代谢和细胞活力的影响。采用乳酸脱氢酶泄漏来监测IGF-I和胰岛素的细胞保护作用。因此，在常氧条件下，两种肽均能减少神经元中乳酸脱氢酶的泄漏。然而，在缺氧条件下，仅在存在胰岛素时才观察到这种保护作用。有趣的是，在缺氧期间，神经元的乳酸脱氢酶泄漏比星形胶质细胞或共培养物少得多。一种可能的解释是神经元中的糖酵解增加。因此，在缺氧期间，神经元中的乳酸生成和葡萄糖消耗增加了数倍，而星形胶质细胞和共培养物仅略有增加。在常氧条件下，胰岛素和IGF-I均能增加星形胶质细胞而非神经元中的葡萄糖代谢，而在缺氧条件下，这种增加不太明显。使用[1-13C]葡萄糖可以证明，在常氧条件下，在胰岛素或IGF-I存在的情况下，星形胶质细胞中线粒体前体生成乳酸的过程受到下调，而神经元中则增加。在缺氧期间不使用这种乳酸生成途径，并且乳酸掺入到C-3位置接近理论最大值50%。
