Oxygen affinity of hemoglobin and peripheral nerve degeneration in experimental diabetes

J Neurol Sci. 1991 Feb;101(2):204-7. doi: 10.1016/0022-510x(91)90047-b.

Abstract

Peripheral neuropathy remains a major complication of diabetes. Numerous etiological theories of metabolic and/or vascular disturbances have been suggested including decreased endoneurial oxygen tension with presumed tissue hypoxia. Increases in the affinity of hemoglobin for oxygen (Hb-O2 affinity) may also produce tissue hypoxia and such Hb-O2 affinity changes have been implicated in the pathogenesis of diabetic microangiopathy. In order to test whether affinity hypoxia might contribute to the development of diabetic peripheral neuropathy, we have utilized a rat model of high and normal Hb-O2 affinity produced by backcrossing animals with increased and decreased levels of 2,3-diphosphoglycerate (DPG). Diabetes was induced in ten high and ten low DPG animals with a tail vein injection of 55 mg/kg streptozotocin (STZ). Five animals in each group were treated with 2.4 U protamine zinc insulin (PZI)/day while the remaining animals were untreated. All rats were killed after 30 days, sections of tibial and sural nerve were rapidly removed and processed for teased fiber analysis. A minimum of 125 axons were assessed per nerve for E degeneration (myelin ovoids) using the classification developed by Dyck et al. Untreated animals, regardless of DPG levels, demonstrated 0% neuropathy. In contrast, all insulin-treated animals showed degeneration (0.4-17%) that inversely correlated with the DPG level (r = -0.59, P less than 0.04). The results of this study suggest that the level of RBC DPG (and presumably the Hb-O2 affinity) with its attendant effect on tissue oxygen release may play a role in the development of peripheral neuropathy in STZ-induced diabetic rats treated with insulin.

MeSH terms

  • 2,3-Diphosphoglycerate
  • Adenosine Triphosphate / blood
  • Animals
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Angiopathies / complications
  • Diabetic Angiopathies / metabolism
  • Diabetic Neuropathies / etiology
  • Diabetic Neuropathies / metabolism*
  • Diabetic Neuropathies / pathology
  • Diphosphoglyceric Acids / blood
  • Erythrocytes / metabolism
  • Hemoglobins / metabolism*
  • Hypoxia / etiology
  • Hypoxia / metabolism
  • Insulin, Long-Acting / pharmacology
  • Insulin, Long-Acting / therapeutic use
  • Male
  • Oxygen / metabolism*
  • Oxyhemoglobins / metabolism
  • Peripheral Nerves / blood supply
  • Peripheral Nerves / drug effects
  • Peripheral Nerves / metabolism*
  • Rats
  • Rats, Inbred Strains / metabolism

Substances

  • Diphosphoglyceric Acids
  • Hemoglobins
  • Insulin, Long-Acting
  • Oxyhemoglobins
  • 2,3-Diphosphoglycerate
  • Adenosine Triphosphate
  • Oxygen