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

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 degrees C, pH 7.4, pO2 approximately 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.

journal_name

Kidney Int

journal_title

Kidney international

authors

Tilton RG,Baier LD,Harlow JE,Smith SR,Ostrow E,Williamson JR

doi

10.1038/ki.1992.121

subject

Has Abstract

pub_date

1992-04-01 00:00:00

pages

778-88

issue

4

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)57550-9

journal_volume

41

pub_type

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