FORMATION OF ADVANCED GLYCATION END (AGE) PRODUCTS IN DIABETES - PREVENTION BY PYRUVATE AND ALPHA-KETO GLUTARATE

Glycation of proteins and their subsequent structural and functional m odifications have been ascribed to play a prominent role in the pathog enesis of several secondary complications of diabetes, such as catarac t and retinopathy. In addition, it plays a role in the generalized age ing process as well. Investigations have been conducted to explore the possibility of preventing the above process by use of pyruvate and al pha-keto glutarate as representatives of physiologically compatible ke to acids. The results demonstrate that both these compounds are effect ive in preventing the initial glycation reaction as well as the format ion of AGE products. Both these compounds also inhibit the generation of high molecular weight aggregates associated with cataract formation . Mechanistically, the preventive effects appear to be due to (1) comp etitive inhibition of glycation by the keto acids and (2) the antioxid ant (radical scavenging) properties of these compounds. The results ar e hence considered useful from the point of view of developing these a nd other keto acid derivatives as pharmacological agents useful in pre venting glycation related protein changes and consequent tissue pathol ogical manifestations.