Linked Life Data

9688898

Source:http://linkedlifedata.com/resource/pubmed/id/9688898

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1 Pt 2
pubmed:dateCreated
1998-8-27
pubmed:abstractText
Alterations in glucose metabolism have been implicated in the cardiovascular complications of diabetes. Previous work in this laboratory demonstrated that hearts from diabetic animals have an elevated cytosolic redox ratio (NADH/NAD+) and that this redox imbalance is probably due to elevated polyol pathway flux. We therefore hypothesized that 1) the elevated cytosolic redox ratio of diabetic hearts could result in inhibition of glycolytic enzymes sensitive to the redox state, 2) polyol pathway inhibition could restore the abnormal glucose metabolism of diabetic hearts, and 3) the relative incorporation of mixed substrates into hearts from diabetic animals would demonstrate less glycolytic and more fatty acid oxidation. Hearts from diabetic (BB/W) and nondiabetic control rats were perfused with buffers containing 13C-labeled substrates, and the metabolism of these hearts was analyzed using 13C NMR spectroscopy. Tissue samples were analyzed for metabolite levels using biochemical assay. Compared with controls, diabetic hearts had glyceraldeyde 3-phosphate levels that were four times greater than nondiabetic hearts and exhibited 91% less 13C labeling of lactate and 92% less 13C labeling of glutamate (P < 0.03). Aldose reductase inhibition with zopolrestat restored the metabolite labeling of diabetic hearts. Diabetic hearts perfused with a mixture of substrates used 53% more acetate than nondiabetic control hearts (P < 0.05), and aldose reductase inhibition lowered the acetate utilization of diabetic hearts by 9% (P < 0.05). These data suggest that glycolytic flux in diabetic hearts is inhibited at glyceraldehyde-3-phosphate dehydrogenase and that inhibition of the polyol pathway with zopolrestat increases glycolytic flux in these hearts. Furthermore, hearts from diabetic animals showed a marked dependence on fatty acids for substrate utilization compared with nondiabetic controls, consistent with inhibition of the pyruvate dehydrogenase complex in diabetic hearts.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H75-83
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9688898-Aldehyde Reductase, pubmed-meshheading:9688898-Animals, pubmed-meshheading:9688898-Benzothiazoles, pubmed-meshheading:9688898-Blood Pressure, pubmed-meshheading:9688898-Citric Acid Cycle, pubmed-meshheading:9688898-Diabetes Mellitus, Type 1, pubmed-meshheading:9688898-Enzyme Inhibitors, pubmed-meshheading:9688898-Glucose, pubmed-meshheading:9688898-Glyceraldehyde 3-Phosphate, pubmed-meshheading:9688898-Glycolysis, pubmed-meshheading:9688898-Heart, pubmed-meshheading:9688898-Heart Rate, pubmed-meshheading:9688898-Models, Chemical, pubmed-meshheading:9688898-Myocardium, pubmed-meshheading:9688898-Phthalazines, pubmed-meshheading:9688898-Rats, pubmed-meshheading:9688898-Rats, Inbred BB, pubmed-meshheading:9688898-Reference Values, pubmed-meshheading:9688898-Thiazoles
pubmed:year
1998
pubmed:articleTitle
Aldose reductase inhibition improves altered glucose metabolism of isolated diabetic rat hearts.
pubmed:affiliation
Division of Cardiovascular Medicine, University of California, Davis, California 95616, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't