**3.2 AGEs and insulin resistance in vivo**

AGEs burden is also shown to be associated with impaired endothelial function 41-44. Endothelial dysfunction could be profoundly associated with less insulin delivery to the skeletal muscle interstitium, leading to decreased insulin-stimulated glucose uptake by the skeletal muscle 45-49, which is implicated in the pathogenesis of insulin resistance. More directly, the restriction of the AGE content in standard mouse diets was found to markedly improve insulin resistance in obese *db/db*(++) mice 50. More recent observation shows targeted reduction of the advanced glycation pathway improved renal function in obesity 51. This interesting observation was further supported by the findings that the development of insulin resistance and type 2 diabetes during prolonged high-fat feeding are linked to the excess AGEs/advanced lipoxidation end products inherent in fatty diets 52.
