Advanced glycation end products and insulin resistance in diabetic nephropathy.

Abstract

Insulin resistance is a central hallmark that connects the metabolic syndrome and diabetes to the resultant formation of advanced glycation end products (AGEs), which further results in the complications of diabetes, including diabetic nephropathy. Several factors play an important role as an inducer to diabetic nephropathy, and AGEs elicit their harmful effects via interacting with the receptor for AGEs Receptor for AGEs, by induction of pro-inflammatory cytokines, oxidative stress, endoplasmic reticulum stress and fibrosis in the kidney tissues leading to the loss of renal function. Insulin resistance results in the activation of other alternate pathways governed by insulin, which results in the hypertrophy of the renal cells and tissue remodeling. Apart from the glucose uptake and disposal, insulin dependent PI3K and Akt also upregulate the expression of endothelial nitric oxide synthase, that results in increasing the bioavailability of nitric oxide in the vascular endothelium, which further results in tissue fibrosis. Considering the global prevalence of diabetic nephropathy, and the impact of protein glycation, various inhibitors and treatment avenues are being developed, to prevent the progression of diabetic complications. In this chapter, we discuss the role of glycation in insulin resistance and further its impact on the kidney.