Altered metabolism and superoxide generation in neural tissue of rat embryos exposed to high glucose.

Oxygen uptake and glucose utilization of embryonic and fetal neural tissue of normal and diabetic rat pregnancy were studied. Exposure to 50 mM glucose inhibited oxygen uptake of embryonic neural tissue of normal rats by 28% at gestational day 9 (P < 0.001) and 20% at days 10-12 and 15 (P < 0.001) and stimulated glucose utilization by 132% at day 9 (P < 0.001), 50% at days 10 and 11 (P < 0.01), 168% at day 12 (P < 0.001), and 338% at day 15 (P < 0.001), indicating a Crabtree effect. The glucose-altered metabolism led to production of superoxide by the tissue, which was 1.8 to 2.4 nmol.h-1.microgram DNA-1 at days 9-12 and 1.2 nmol.h-1.microgram DNA-1 at day 15. The embryonic neural tissue of diabetic rats showed a diminished metabolic sensitivity to high glucose exposure, suggesting an impaired mitochondrial function. Consequently, the glucose-induced superoxide production was not detected in the tissue of embryos of diabetic rats. The data suggest that high concentration of glucose alters embryonic and fetal metabolism and causes generation of superoxide. Prolonged duration of the glucose-induced metabolic changes may impair cellular function and lead to embryonic dysmorphogenesis.