Huangqi (Astragalus) decoction ameliorates diabetic nephropathy via IRS1-PI3K-GLUT signaling pathway

Huangqi decoction (HD) is a prescription for the treatment of diabetes in traditional Chinese medicine. The study was aimed to investigate the effect of HD on diabetic nephropathy. Male diabetic db/db mice which develop diabetic nephropathy spontanously and non-diabetic db/m control mice were used in the current study, and received the treatment of HD for 14 consecutive weeks. HD treatment dose-dependently decreased the body weight, urine volume, water intake and food intake, improved glucose tolerance and insulin resistance, and lowered blood glucose, serum glycosylated hemoglobin, insulin and insulin resistance index in db/db mice. The db/db mice also showed low levels of serum creatinine, blood urea nitrogen and urine albumin, and improved renal functions such as glomerular filtration rate after HD treatment. Histological examination showed that HD treatment prevented the deterioration of basement membrane of glomerular capillary, mesangial matrix and renal tubular lumen in the db/db mice. Through examining the cell signaling pathways which might be involved in the pathology of diabetic nephropathy, we found that HD treatment activated phospho-IR^Y1361, phospho-IRS1^Y896, phospho-PI3K, and inhibited phospho-IRS1^S636/639, phospho-AKT^T308 and phospho-AKT^S473. HD treatment abolished the change in the expression of glucose transporters in the diabetic kidney with an increase in GLUT4 but decrease in GLUT1 expression in the kidney in a dose-dependent manner. Our study suggests that HD prevents the development of diabetes and improves renal function in the db/db mice and HD regulation of the IRS1-PI3K-GLUT signaling pathway significantly improves diabetic nephropathy.