Diabetes-induced glomerular dysfunction: Links to a more reduced cytosolic ratio of NADH/NAD+

Ronald G. Tilton, Lisa D. Baier, Judith E. Harlow, Samuel R. Smith, Eva Ostrow, Joseph R. Williamson

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

These studies were undertaken to examine effects of elevated glucose levels on glycolysis, sorbitol pathway activity, and the cytosolic redox state of NADH/NAD+ in isolated glomeruli. Blood-free glomeruli were isolated from kidneys of male, Sprague-Dawley rats using standard sieving techniques, then incubated for one hour at 37°C, pH 7.4, p02 ∼500 torr, in Krebs bicarbonate/Hepes buffer containing 5 or 30 mM glucose. Elevated glucose levels increased glucose 6-phosphate, fructose 6-phosphate, total triose phosphates, lactate, the lactate/pyruvate ratio, sorbitol, and fructose, but did not affect sn-glycerol 3-phosphate, pyruvate, or myo-inositol levels. The more reduced glomerular cytosolic redox state (manifested by the tissue lactate/pyruvate ratio) induced by 30 mM glucose was completely abrogated by aldose reductase inhibitors added to the diet two to seven days prior to glomerular isolation. These observations, coupled with evidence linking glucose- and diabetes-induced glomerular dysfunction to increased sorbitol pathway metabolism, support the hypothesis that metabolic imbalances associated with a more reduced ratio of cytosolic NADH/NAD+ (resulting from increased glucose metabolism via the sorbitol pathway) play an important role in mediating glucose- and diabetes-induced glomerular dysfunction.

Original languageEnglish (US)
Pages (from-to)778-788
Number of pages11
JournalKidney International
Volume41
Issue number4
DOIs
StatePublished - Apr 1992

ASJC Scopus subject areas

  • Nephrology

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    Tilton, R. G., Baier, L. D., Harlow, J. E., Smith, S. R., Ostrow, E., & Williamson, J. R. (1992). Diabetes-induced glomerular dysfunction: Links to a more reduced cytosolic ratio of NADH/NAD+. Kidney International, 41(4), 778-788. https://doi.org/10.1038/ki.1992.121