title: 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.
authors.affiliation: Medical Clinic V, School of Clinical Medicine, Mannheim, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
authors.forename: Xueliang
authors.initials: X
authors.lastname: Du
authors.forename: Diane
authors.initials: D
authors.lastname: Edelstein
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumura
authors.forename: Qida
authors.initials: Q
authors.lastname: Ju
authors.forename: Jihong
authors.initials: J
authors.lastname: Lin
authors.forename: Angelika
authors.initials: A
authors.lastname: Bierhaus
authors.forename: Peter
authors.initials: P
authors.lastname: Nawroth
authors.forename: Dieter
authors.initials: D
authors.lastname: Hannak
authors.forename: Michael
authors.initials: M
authors.lastname: Neumaier
authors.forename: Regine
authors.initials: R
authors.lastname: Bergfeld
authors.forename: Ida
authors.initials: I
authors.lastname: Giardino
authors.forename: Michael
authors.initials: M
authors.lastname: Brownlee
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000209:etiology / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism / Q000473:pathology; D013831:Thiamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D014174:Transketolase / Q000378:metabolism*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D014537:Uridine Diphosphate N-Acetylglucosamine; D014174:Transketolase; D011493:Protein Kinase C; D005947:Glucose; D013831:Thiamine; C013835:benphothiamine