Source:http://linkedlifedata.com/resource/pubmed/id/12882930
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2003-7-28
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pubmed:abstractText |
Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that stimulation of the reductive pentosephosphate pathway by high-dose therapy with thiamine and the thiamine monophosphate derivative benfotiamine countered the accumulation of triosephosphates in experimental diabetes and inhibited the development of incipient nephropathy. High-dose thiamine and benfotiamine therapy increased transketolase expression in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate, and strongly inhibited the development of microalbuminuria. This was associated with decreased activation of protein kinase C and decreased protein glycation and oxidative stress-three major pathways of biochemical dysfunction in hyperglycemia. Benfotiamine also inhibited diabetes-induced hyperfiltration. This was achieved without change in elevated plasma glucose concentration and glycated hemoglobin in the diabetic state. High-dose thiamine and benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0012-1797
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2110-20
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12882930-Albuminuria,
pubmed-meshheading:12882930-Animals,
pubmed-meshheading:12882930-Chelating Agents,
pubmed-meshheading:12882930-Diabetes Mellitus, Experimental,
pubmed-meshheading:12882930-Diabetic Nephropathies,
pubmed-meshheading:12882930-Dose-Response Relationship, Drug,
pubmed-meshheading:12882930-Male,
pubmed-meshheading:12882930-Pentose Phosphate Pathway,
pubmed-meshheading:12882930-Rats,
pubmed-meshheading:12882930-Rats, Sprague-Dawley,
pubmed-meshheading:12882930-Thiamine,
pubmed-meshheading:12882930-Transketolase
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pubmed:year |
2003
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pubmed:articleTitle |
Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine.
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pubmed:affiliation |
Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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