Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy

Hans Peter Hammes, Xueliang Du, Diane Edelstein, Tetsuya Taguchi, Takeshi Matsumura, Qida Ju, Jihong Lin, Angelika Bierhaus, Peter Nawroth, Dieter Hannak, Michael Neumaier, Regine Bergfeld, Ida Giardino, Michael Brownlee

Research output: Contribution to journalArticle

613 Scopus citations

Abstract

Three of the major biochemical pathways implicated in the pathogenesis of hyperglycemia induced vascular damage (the hexosamine pathway, the advanced glycation end product (AGE) formation pathway and the diacylglycerol (DAG)-protein kinase C (PKC) pathway) are activated by Increased availability of the glycolytic metabolites glyceraldehyde-3-phosphate and fructose- 6-phosphate. We have discovered that the lipid-soluble thiamine derivative benfotiamine can inhibit these three pathways, as well as hyperglycemia-associated NF-κB activation, by activating the pentose phosphate pathway enzyme transketolase, which converts glyceraldehyde-3-phosphate and fructose-6-phosphate into pentose-5-phosphates and other sugars. In retinas of diabetic animals, benfotlamine treatment inhibited these three pathways and NF-κB activation by activating transketolase, and also prevented experimental diabetic retinopathy. The ability of benfotiamine to inhibit three major pathways simultaneously might be clinically useful in preventing the development and progression of diabetic complications.

Original languageEnglish (US)
Pages (from-to)294-299
Number of pages6
JournalNature Medicine
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hammes, H. P., Du, X., Edelstein, D., Taguchi, T., Matsumura, T., Ju, Q., Lin, J., Bierhaus, A., Nawroth, P., Hannak, D., Neumaier, M., Bergfeld, R., Giardino, I., & Brownlee, M. (2003). Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nature Medicine, 9(3), 294-299. https://doi.org/10.1038/nm834