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

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

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

Full description

Saved in:
Bibliographic Details
Published in:Kidney international Vol. 41; no. 4; pp. 778 - 788
Main Authors: Tilton, Ronald G., Baier, Lisa D., Harlow, Judith E., Smith, Samuel R., Ostrow, Eva, Williamson, Joseph R.
Format: Journal Article
Language:English
Published: New York, NY Elsevier Inc 01-04-1992
Nature Publishing
Subjects:
Aldehyde Reductase - antagonists & inhibitors
Animals
Biological and medical sciences
Blood Glucose - analysis
Cytosol - metabolism
Diabetic Nephropathies - metabolism
Diabetic Nephropathies - physiopathology
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
In Vitro Techniques
Kidney Glomerulus - metabolism
Kidney Glomerulus - physiopathology
Male
Medical sciences
NAD - metabolism
Oxidation-Reduction
Rats
Rats, Inbred Strains
Endocrinopathy
Glomerulonephritis
Animal model
Urinary system disease
Pathophysiology
Rat
Diabetes mellitus
Rodentia
Renal disease
Kidney
Isolated organ
Renal glomerulus
Vertebrata
Metabolic disorder
Mammalia
Animal
Glycolysis
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Diabetes-induced glomerular dysfunction: Links to a more reduced cytosolic ratio of NADH/NAD+. 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, pO2 ∼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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0085-2538
1523-1755
DOI:10.1038/ki.1992.121