NEW ASPECTS OF LACTATE METABOLISM - IGF-I AND INSULIN REGULATE MITOCHONDRIAL-FUNCTION IN CULTURED BRAIN-CELLS DURING NORMOXIA AND HYPOXIA

Using C-13 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 hypoxi a. Lactate dehydrogenase leakage was used to monitor the cytoprotectiv e effects of IGF-I and insulin. Thus, during normoxia both peptides de creased LDH leakage from neurons. During hypoxia, however, this protec tion was only observed when insulin was present, Interestingly, neuron s showed much less LDH leakage during hypoxia than astrocytes or cocul tures, A possible explanation could be an increased glycolysis in neur ons. Thus, lactate production and glucose consumption were increased s everalfold in neurons during hypoxia whereas astrocytes and cocultures only showed a slight increase. Both insulin and IGF-I increased gluco se metabolism during normoxia in astrocytes but not in neurons, wherea s during hypoxia this increase was less pronounced. Using [1-C-13]gluc ose it could be demonstrated that production of lactate from mitochond rial precursors was, in the presence of insulin or IGF-I, down regulat ed in astrocytes but increased in neurons during normoxia. This route for lactate production was not used during hypoxia and incorporation i nto the C-3 position of lactate approached the theoretical maximum of 50%.