Pathogenesis and treatment of insulin resistance in chronic kidney disease and interventional effects of Chinese herbal medicine / 中国中药杂志

ABSTRACT

The kidney is the target organ of insulin with abundant insulin receptors. Thereinto,the renal intrinsic cells including glomerular podocytes,endothelial cells,mesangial cells,renal tubular epitheliums and collecting duct epithelial cells are all highly sensitive to insulin as the effector cells. Furthermore,the structural and functional abnormalities of these cells are closely related to insulin and its receptors activity. It is reported that the chronic kidney disease（CKD）patients have systemic or renal insulin resistance（IR）. IR is not only the pathogenic factor of CKD but also one of the mechanisms of CKD progression. The pathogenic factors of IR in the CKD patients include the systemic factors and the local factors in muscles and fat cells. The pathogenesis of IR is related to glomeruli,proximal tubules,collecting ducts and corresponding renal intrinsic cells such as podocytes,mesangial cells,renal tubular epitheliums and collecting duct epithelial cells. IR-related signaling pathways include insulin receptor substrate（IRS）/phosphatidylinositol 3 kinase（PI3K）/serine threonine kinase（Akt）pathway,adenosine monophosphate activated protein kinase（AMPK）pathway,glucose transporter4（GLUT4）pathway,nuclear factor（NF）-κB pathway and mitogen activated protein kinase（MAPK）pathway. Among them,IRS1/PI3K/Akt2 is the main signaling pathway of IR in podocytes of glomeruli, thus intervening its activity can improve podocyte injury. In clinic,some classical oral hypoglycemic agents and diuretic including metformin,rosiglitazone,glibenclamide,thiazolidinedione and spironolactone,as well as some extracts from Chinese herbal medicines including astragalus polysaccharides,quercetin,puerarin,emodin,berberine,curcumin and geniposide can both affect insulin and its receptor activity,and regulate IR-related signaling pathways,thereby ameliorating IR and CKD progression. Overall,the pharmacological studies based on IR-related signaling pathways in the renal intrinsic cells of CKD will become one of the developmental directions in the future.