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1997 ; 5
(4
): 365-391
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Glycation, oxidation, and lipoxidation in the development of the complications of
diabetes: a carbonyl stress hypothesis
#MMPMID26366051
Lyons TJ
; Jenkins AJ
Diabetes Rev (Alex)
1997[]; 5
(4
): 365-391
PMID26366051
show ga
Modifications of extant plasma proteins, structural proteins, and other
macromolecules are enhanced in diabetes because of increased glycation (secondary
to increased glucose concentrations) and perhaps because of increased oxidative
stress. Increased glycation is present from the time of onset of diabetes, but
the relation between diabetes and oxidative stress is less clear: increased
oxidative stress may occur later in the course of disease, as vascular damage
becomes established, or it may be a feature of uncomplicated diabetes. The
combined effects of protein modification by glycation and oxidation may
contribute to the development of accelerated atherosclerosis in diabetes and to
the development of microvascular complications. Thus, even if not increased by
diabetes, variations in oxidative stress may modulate the consequences of
hyperglycemia in individual diabetic patients. In this review, the close
interaction between glycation and oxidative processes is discussed, and the theme
is developed that the most significant modifications of proteins are the result
of interactions with reactive carbonyl groups. While glucose itself contains a
carbonyl group that is involved in the initial glycation reaction, the most
important and reactive carbonyls are formed by free radical-oxidation reactions
damaging either carbohydrates (including glucose itself) or lipids. The resulting
carbonyl-containing intermediate products then modify proteins, yielding
"glycoxidation" and "lipoxidation" products, respectively. This common pathway
for glucose and lipid-mediated stress, which may contribute to diabetic
complications, is the basis for the carbonyl stress hypothesis for the
development of diabetic complications.