Oxygen affinity of hemoglobin and peripheral nerve degeneration in experimental diabetes.
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.
Farber
S D
SD
Indiana University School of Medicine, Indianapolis.
Farber
M O
MO
Brewer
G
G
Magnes
C J
CJ
Peterson
R G
RG
D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000150:complications / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004163:Diphosphoglyceric Acids / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism; D049528:Insulin, Long-Acting / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000378:metabolism; D010525:Peripheral Nerves / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism
D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D049528:Insulin, Long-Acting; D010108:Oxyhemoglobins; D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate; D010100:Oxygen