Vascular complications are among the most serious manifestations of diabetes. Atherosclerosis
is the main cause of reduced life quality and expectancy in diabetics, whereas diabetic
nephropathy and retinopathy are the most common causes of end-stage renal disease and blindness.
An effective therapeutic approach to prevent vascular complications should counteract the mechanisms
of injury. Among them, the toxic effects of Advanced Glycation (AGEs) and Lipoxidation
(ALEs) end-products are well-recognized contributors to these sequelae. L-carnosine (β-alanyl-Lhistidine)
acts as a quencher of the AGE/ALE precursors Reactive Carbonyl Species (RCS), which
are highly reactive aldehydes derived from oxidative and non-oxidative modifications of sugars and
lipids. Consistently, L-carnosine was found to be effective in several disease models in which
glyco/lipoxidation plays a central pathogenic role. Unfortunately, in humans, L-carnosine is rapidly
inactivated by serum carnosinase. Therefore, the search for carnosinase-resistant derivatives of Lcarnosine
represents a suitable strategy against carbonyl stress-dependent disorders, particularly
diabetic vascular complications. In this review, we present and discuss available data on the efficacy
of L-carnosine and its derivatives in preventing vascular complications in rodent models of diabetes
and metabolic syndrome. We also discuss genetic findings providing evidence for the involvement
of the carnosinase/L-carnosine system in the risk of developing diabetic nephropathy and for preferring
the use of carnosinase-resistant compounds in human disease. The availability of therapeutic
strategies capable to prevent both long-term glucose toxicity, resulting from insufficient glucoselowering
therapy, and lipotoxicity may help reduce the clinical and economic burden of vascular
complications of diabetes and related metabolic disorders.
Keywords: Diabetes, vascular complications, atherosclerosis, diabetic nephropathy, carnosine, reactive carbonyl
species, advanced glycation end-products, metabolic memory.
Maillard, L.C. Action of amino acids on sugars: formation of melanoidins in a methodical way. Compt. Rend., 1912, 154, 66.
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