The Renoprotective Effect Of Low-protein Calorie-restricted Diet In Type 2 Diabetic Rats

Objective To investigate the renoprotective effect of low-protein calorie-restricted diet in type 2 diabetic rats and its possible mechanisms.Methods The type 2 diabetic rat model was induced with a combination of high-fat diet and low-dose streptozotocin.The diabetic rats were randomly divided into 3 groups,normal protein(NP,20% protein)group,low protein(LP,8% protein)group and LPCR(8% protein,30% restriction)group.Normal control(NC)group was also established.After 4 weeks of dietary intervention,related physical and biochemical parameters,kidney-to-body weight ratio,mesangial matrix expansion,podocyte density,and glomerular basement membrane(GBM)thickness,as well as the number of autophagic vacuoles in podocytes were evaluated.The protein expressions of microtubule-associated protein light chain 3(LC3),AMP-activated protein kinase(AMPK),phosphorylated AMPK(p-AMPK),mechanistic target of rapamycin(m TOR),and phosphorylated m TOR(p-m TOR)in the glomeruli were examined by western blot analysis.Results These diabetic rats developed the features of early-stage diabetic nephropathy,as shown by microalbuminuria,elevated kidney-to-body weight ratio,accumulation of mesangial matrix,and diffuse thickening of the GBM.Treatment with an LPCR diet for 4 weeks induced a significant reduction in fasting blood glucose levels,Homeostasis model assessment of insulin resistance(HOMA-IR),microalbuminuria,mesangial matrix expansion,and GBM thickness compared with the NP group.No significant difference was noted in the serum creatinine and creatinine clearance of diabetic rats compared to those of non-diabetic rats.The decreased podocyte density and reduced number of autophagic vacuoles in podocytes observed in the diabetic rats were reversed after being fed the LPCR diet.The expression of LC3-II/LC3-I in the glomeruli of diabetic rats was lower than that in non-diabetic rats;however,this difference was not statistically significant.Notably,a remarkable upregulation of LC3-II/LC3-I was observed in the glomeruli of diabetic rats fed an LPCR diet.The ratio of p AMPK/AMPK was significantly lower in the NP group than in the NC group,while the ratio of pm TOR/m TOR was significantly elevated.However,treatment with LPCR diet for 4 weeks induced a remarkable upregulation of p AMPK/AMPK and a significant downregulation of pm TOR/m TOR compared with that in the NP group.Conclusions These findings suggest that an LPCR diet can ameliorate renal injury,including podocyte injury,in type 2 diabetic rats,and the renoprotective effect appears to be linked to the activation of podocyte autophagy via regulation of the m TOR/AMPK signaling pathway.