Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy
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-kappaB 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, benfotiamine treatment inhibited these three pathways and NF-kappaB 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.
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Higher iron intake, especially haem iron, and higher iron status are associated with increased risk of type 2 diabetes, atherosclerosis and coronary heart disease, although the literature is not fully consistent.
“There is some epidemiological evidence that higher Fe intake, particularly that of haem Fe, and higher Fe status are associated with increased risk of type 2 diabetes, atherosclerosis and CHD (702 -714) , although not all of the literature is consistent.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [702]
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Self-citation
- Authors
- 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.
- Affiliations
- Albert Einstein College of Medicine (US)
- Heidelberg University (DE)
- Justus-Liebig-Universität Gießen (DE)
- Corresponding author
- Brownlee, Michael
- ORCID
- Venue
- Nature Medicine
- Published
- 2003-02-18
- Volume
- 9
- Issue
- 3
- Pages
- 294-299
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2066779642
- Cited by
- 785
- References
- 32
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 13 · 2023: 18 · 2022: 29 · 2021: 31 · 2020: 31 · 2019: 29 · 2018: 33 · 2017: 34 · 2016: 32 · 2015: 35 · 2014: 32 · 2013: 36 · 2012: 37
- FWCI
- 26.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Keywords
- benfotiamine, diabetic retinopathy, hyperglycemia, hexosamine biosynthetic pathway, advanced glycation end products, transketolase, pentose phosphate pathway, NF-κB activation, glyceraldehyde-3-phosphate, fructose-6-phosphate, thiamine derivatives, diabetes complications
- MeSH terms
- Animals, Cattle, Cells, Cultured, Diabetes Mellitus, Experimental, Diabetic Retinopathy, Endothelium, Vascular, Enzyme Activation, Glucose, Humans, Hyperglycemia, Male, Protein Kinase C, Random Allocation, Retina, Thiamine, Transketolase, Uridine Diphosphate N-Acetylglucosamine, NF-kappa B, Glycation End Products, Advanced, Rats, Wistar, Rats
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