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

Nat Med. 2003 Mar;9(3):294-9. doi: 10.1038/nm834. Epub 2003 Feb 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Cells, Cultured
  • Diabetes Mellitus, Experimental
  • Diabetic Retinopathy / etiology
  • Diabetic Retinopathy / prevention & control*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Enzyme Activation
  • Glucose / pharmacology
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Hyperglycemia / complications
  • Hyperglycemia / physiopathology*
  • Male
  • NF-kappa B / metabolism
  • Protein Kinase C / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Retina / metabolism
  • Retina / pathology
  • Thiamine / analogs & derivatives*
  • Thiamine / pharmacology
  • Thiamine / therapeutic use*
  • Transketolase / metabolism*
  • Uridine Diphosphate N-Acetylglucosamine / metabolism

Substances

  • Glycation End Products, Advanced
  • NF-kappa B
  • Uridine Diphosphate N-Acetylglucosamine
  • Transketolase
  • Protein Kinase C
  • Glucose
  • Thiamine
  • benphothiamine