Taurine ameliorates the progression of diabetic nephropathy in type 2 diabetic rat model

Abstract

Diabetic nephropathy is the most common diabetic microvascular complication and the most common cause of end-stage renal disease. It is believed to be caused by diverse factors, and a variety of mechanisms have been suggested. The overexpression of vascular endothelial growth factor (VEGF) is known to participate in the pathogenesis of diabetic nephropathy. Taurine has some beneficial effects on diabetic nephropathy, but its mechanisms are still unknown. In the present study, the preventive effect and mechanism of taurine on diabetic nephropathy were investigated.Taurine was administered to Otsuka-Long-Evans-Tokushima fatty (OLETF) rats during 20 weeks. Blood glucose and urine albumin creatinine ratio (ACR) were measured. Glomerular basement membrane (GBM) thickness and slit pore numbers of podocytes were measured by electron microscopy. Renal VEGF mRNA and protein synthesis were evaluated by quantitative real time-polymerase chain reaction (qRT-PCR) and western blot immunostaining. Nephrin and VEGF expression were determined in podocytes cultured with high glucose. Fasting blood glucose, twenty four hours urinary albumin and ACR were reduced, and insulin and homeostasis model assessment of beta-cell function (HOMA-β) were increased in taurine treated diabetic group compared with those in diabetic control group. In taurine treated diabetic group, GBM thickness was decreased and open slit pore numbers were increased. Taurine effectively lowered the elevated VEGF mRNA levels in diabetic group. In podocytes cultured with taurine and high glucose, reactive oxygen species (ROS) formation and VEGF mRNA expression were reversed to the control levels. Nephrin mRNA expressions were increased in podocytes cultured with taurine and high glucose.These data support that taurine prevents the progression of diabetic nephropathy possibly through the recovery of nephrin and insulin secretion, and the downregulation of renal VEGF expression.