Advanced glycation endproducts (AGEs) and chronic complications in diabetes

This review presents insights on the suppression of specific factors of host defense mechanisms with an emphasis on the effects of exogenous AGEs. The data are derived from studies of humans and mice. We propose that the loss of these defenses is the driving force behind the increased oxidative stress and the pathogenesis of both T1DM and T2DM and their complications. Two components of a complex and powerful homeostasis system that provide cell-protective liaisons between cellular AGE receptors (AGER1) and the NAD + -dependent deacetylase sirtuin 1 (SIRT1) are highlighted. An imbalance between host defenses and increased oxidant challenges from the environment appear to form the basis of cell injury that underlies diabetes mellitus. We introduce the concept that reduced levels of AGEs, either by restriction in the diet or by the use of agents block the action(s) of uptake of AGEs as novel costefficient strategies in the prevention and treatment of the current diabetes epidemic.