title: Hyperglycemia preserves brain mitochondrial respiration during anoxia.
abstract: We examined brain mitochondrial function in normo- (5 mM) and hyperglycemic (50 mM) cats after 8 min of anoxia. In anoxic normoglycemic cats, mitochondrial state 3 respiration with NAD-linked substrates glutamate or pyruvate (both plus malate) was inhibited 30-50%. The uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) maximally stimulated respiration, indicating that inhibition of phosphorylation, not impairment of electron transport, substrate transport, or oxidation was present. State 3 respiration with succinate (plus rotenone) was unaffected. Mitochondrial respiratory control ratios trended toward reductions whereas ADP/O ratios remained unchanged. In contrast, brain mitochondria from anoxic hyperglycemic cats showed no such inhibition of state 3 respiration and no differences in function from normo- and hyperglycemic control animals except for trends toward loose coupling. Significantly higher brain tissue glucose concentrations were present in hyperglycemic controls as the only metabolite difference compared to normoglycemic controls. At the end of anoxia, hyperglycemic cats exhibited significantly higher cortical lactate and glucose levels but similarly reduced high-energy phosphate concentrations compared to normoglycemic cats. These results demonstrate that increased availability of glucose to gray matter as a consequence of hyperglycemia maintains normal mitochondrial state 3 respiration during exposure to anoxia. Previous survival studies have shown that lower serum glucose concentrations during anoxia are relatively brain protective. This result indicates that the presently described alterations in mitochondrial respiration must be fully reversible.
mesh_terms: D000818:Animals; D001921:Brain / Q000648:ultrastructure*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002415:Cats; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006943:Hyperglycemia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008293:Malates / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D010101:Oxygen Consumption; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
chemical_list: D005971:Glutamates; D008293:Malates; D011773:Pyruvates; D013386:Succinates; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D018698:Glutamic Acid; C030298:malic acid; D019289:Pyruvic Acid; D019802:Succinic Acid