5+2 Fasting Mode Alleviates Kidney Injury in Type 2 Diabetic Rats by Activating Autophagy Through IRS1/PI3K/AKT Pathway
Objective To explore the mechanism of alleviating kidney injury in type 2 diabetic rats with light fasting mode.Methods SD rats were divided into normal group,diabetes group,light fasting + diabetes group,MHY1485+ light fasting + diabe-tes group and 740 Y-P+ light fasting + diabetes group,with 5 rats in each group.Except the normal group,all the other groups were fed high-fat and high-sugar diet combined with streptomycin to establish type 2 diabetes rat model.In light fasting mode,high-fat and high-sugar diet was fed for 12 h and fasting for 36 h for 12 w.Serum renal function indexes were detected by biochemical detec-tor.Fasting serum insulin(FIN)was detected by ELISA and insulin resistance index(HOMA-IR)was calculated;the mRNA ex-pression levels of IRS1,WT1,LC3B and P62 were detected by qPCR,and the protein expression levels of IRS1,WT1,P62 and LC3Ⅰ/Ⅱ in rat kidney tissues were detected by Western Blot,and the IRS1/PI3K/AKT pathway and autophagy related indicators were studied.The pathological changes were observed by HE and PAS staining,and the expressions of P62 and LC3B were detected by im-munohistochemistry;finally,the apoptosis of renal tissue was evaluated by Tunel staining.Results Compared with the normal group,the serum creatinine(Scr),urea nitrogen(BUN),triglyceride(TG),total cholesterol(TCHO),serum free fatty acid(FFA),fasting FINS,and HOMA-IR in the diabetes group were all increased;After fasting diet mode,the content of the above in-dicators decreased.At the same time,qPCR and Western Blot results showed that compared with the diabetes group,IRS1 was down-regulated in the light fasting mode + diabetes group,and the phosphorylation levels of PI3K and AKT were reduced,thus affecting the increase of LC3B expression and the decrease of P62 expression,which resulted in the improvement of autophagy activity in the kidney tissue,which was consistent with the results of immunohistochemistry;pathological staining showed that fasting diet reduced renal tissue damage and alleviated apoptosis.From the up-regulation of WT1,it can also be seen that podocyte damage also recov-ered.Conclusion Fasting diet mode can improve autophagy activity by up-regulating IRS1 and activating PI3K/AKT pathway,which can alleviate renal injury in type 2 diabetes rats.Alleviating renal tissue damage is of great significance for delaying the develop-ment of diabetic nephropathy.
万方数据
维普
