Aktivace polyolové metabolické dráhy
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Při diabetické hyperglykemii vstupuje Glc do buněk inzulin-non-dependentních (pericyty kapilár a neurony). Aldosareduktasa katalyzuje dehydrogenaci Glc a tvoří se D-glucitol.Reakce spotřebovává NADPH, který je potřebný pro udržování hladiny nitrobuněčného glutathionu,důležitého antioxidantu. Stav zvýšeného poměru NADP+/NADPH se také nazývá diabetická pseudohypoxie.
Působením polyoldehydrogenasy (iditoldehydrogenasy) dochází k přeměně D-glucitolu na fruktozu.Polyoldehydrogenasa vykazuje vysokou aktivitu v hepatocytech, spermiích (Fru je hlavním zdrojem energie) a ovariálních buňkách.Naopak malá je její aktivita v retině, lens crystallina, ledvinných tubulech a periferních nervech, tj.tkáních, které jsou na inzulin necitlivé.
Glucitol nedifunduje snadno buněčnými membránami, a proto se hromadí a vyvolává zvýšení osmotického tlaku a tím ICT, čímž dochází k destrukci buněčných struktur.Krystaliny v takto vysoce osmotickém prostředí denaturují a vytvářejí ložiska silně rozptylující světlo.Tak vzniká diabetická katarakta, retinopatie a neuropatie.
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