In the last decade, increasing attention has been paid to the role of advanced glycation endproducts (AGEs). Methylglyoxal, formed from the spontaneous degradation of the triosephosphates, is a highly potent glycating agent. It has been shown that arginine-derived hydroimidazlone, MG-H1, is the most physiologically relevant MG-derived AGE, typically accounting for >90% adducts formed in vitro and in vivo. Both protein-bound and -free AGEs have been shown to be significantly elevated in in experimental models of diabetes and in diabetic patients.
Studies have also shown that there is an association between AGES and diabetic complications, an association which is independent of blood glucose. It has been suggested that the increase in MG and its associated AGEs is as a consequence of the loss of detoxification via Glyoxalase I (Glo1).The balance, therefore, between the production and detoxification of MG may provide a decisive factor in the development and progression of the diabetic complications. The purpose of this project is to address this concept in more detail, and provide a greater understanding of the factors which influence the balance between production and detoxification.