Interactions between advanced glycation and oxidative stress in diabetic renal and cardiac complications

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Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's ability to renew these protein, hence causing accelration of the ageing process. In fact, it is estimated that this process occurs almost fifty times faster in diabetes. These sticky complexes accumulate in tissues causing disruption ot the normal tissue structure. Our group has a drug which can act as scissors and cut the sticky sugar off the proteins allowing it to be turned over. Unfortunately this does not fix all of the damage. These AGE molecules are involved in a number of other harmful processes including the production of toxic oxygen derived molecules which are harmful byproducts of diabetes. While these oxygen 'radicals' have been implicated in heart attack and stroke their source has remained a mystery in diabetes. Previously, the only way to remove these molecules was to mop them up with antioxidants such as Vitamin E. Antioxidants work slowly and so some damage is already done before they 'detoxify' these oxygen radicals. We propose to use combinations of medicines to see if we can achieve more effective protection against these processes in experimental diabetes. This may provide new therapies for threatment of kidney and heart disease in diabetes.