Diabetic neuropathy in db/db mice develops independently of changes in ATPase and aldose reductase - A biochemical and immunohistochemical study

R. Bianchi, C. Marelli, P. Marini, M. Fabris, C. Triban, M. G. Fiori

Research output: Contribution to journalArticlepeer-review

Abstract

ATPase activity was investigated in sciatic and optic nerves of female mutant diabetic C57Bl/Ks (db/db) mice and age-matched control mice (db/m and m/m). Nerves from animals aged 50, 70, 125, 180 and 280 days were assayed in vitro for ATPase activity in the presence or absence of ouabain: the ouabain-sensitive fraction contained Na+,K+-ATPase. Enzymatic activity was compared within and between age-matched groups. No significant difference in Na+,K+-ATPase activity was detected between the diabetic and control mice, whether expressed as μmol Pi/h-1 formed per gramme wet weight or per nerve (protein content). The activity decreased by about 25% in both the sciatic and optic nerves of the oldest animals. These results were strikingly similar in all groups, regardless of the type of nerve examined, confirming that the development of neuropathy in this animal model is unrelated to the postulated derangement of Na+,K+-ATPase activity. Among possible explanations, a lack of polyol pathway activation was investigated by staining the sciatic nerves of animals from all groups with the peroxidase-antiperoxidase procedure using a polyclonal antiserum raised against the enzyme aldose reductase. Histological sections of all nerves were consistently negative, suggesting that these animals actually lack the enzyme involved in activating the self-perpetuating metabolic cycle leading to deranged nerve function. The db/db mouse appears to present particular biochemical changes which merit attention with a view to clarifying the pathogenesis of diabetic neuropathy.

Original languageEnglish
Pages (from-to)131-136
Number of pages6
JournalDiabetologia
Volume33
Issue number3
DOIs
Publication statusPublished - Mar 1990

Keywords

  • aldose reductase
  • diabetic mutant mice
  • immunohistochemistry
  • Na,K-ATPase
  • optic nerve
  • sciatic nerve

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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