The paradox between resistance to hypoxia and liability to hypoxic damage in hyperglycemic peripheral nerves. Evidence for glycolysis involvement.
Isolated ventral and dorsal rat spinal roots incubated in normal (2.5 mM) or high glucose (25 mM) concentrations or in high concentrations of other hexoses were exposed transiently to hypoxia (30 min) in a solution of low buffering power. Compound nerve action potentials, extracellular direct current potentials, and interstitial pH were continuously recorded before, during, and after hypoxia. Ventral roots incubated in 25 mM D-glucose showed resistance to hypoxia. Dorsal roots, on the other hand, revealed electrophysiological damage by hyperglycemic hypoxia as indicated by a lack of posthypoxic recovery. In both types of spinal roots, interstitial acidification was most pronounced during hyperglycemic hypoxia. The changes in the sensitivity to hypoxia induced by high concentrations of D-glucose were imitated by high concentrations of D-mannose. In contrast, D-galactose, L-glucose, D-fructose, and L-fucose did not have such effects. Resistance to hypoxia, hypoxia-generated interstitial acidification, and hypoxia-induced electrophysiological damage were absent after pharmacological inhibition of nerve glycolysis with iodoacetate. These observations indicate 1) that enhanced anaerobic glycolysis produces resistance to hypoxia in hyperglycemic peripheral nerves and 2) that acidification may impair the function of peripheral axons when anaerobic glycolysis proceeds in a tissue with reduced buffering power.
Department of Physiology, University of Munich, Germany.
U
U
Schneider
W
W
Niedermeier
P
P
Grafe
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015687:Cell Hypoxia; D005947:Glucose / Q000494:pharmacology*; D006019:Glycolysis; D006601:Hexoses / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006943:Hyperglycemia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010525:Peripheral Nerves / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology*
D006601:Hexoses; D005947:Glucose