Cell Death Dis: AMPK agonists alleviate tubular interstitial fibrosis by activating autophagy in diabetic mice induced by high-fat and streptozotocin.

Background: Diabetic nephropathy (DN) is one of the most serious microvascular complications in diabetic patients
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Approximately 30-40% of diabetes (DM) patients develop kidney disease and progress to kidney damage

Diabetic nephropathy (DN) is one of the most serious microvascular complications in diabetic patients

Methods: In this study, a mouse model of type 2 diabetes induced by high-fat diet (HFD) and streptozotocin (STZ) and HK-2 cells were used
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Metformin was taken orally (200 mg/kg/d) for 24 weeks

Results: We found that the expression of p-AMPK, PINK1, Parkin, LC3II and ATG5 in the kidney tissue of diabetic mice was significantly reduced
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Metformin can reduce blood creatinine and urine protein levels in HFD/STZ-induced diabetic mice, and reduce oxidative damage and fibrosis of the kidney

Figure 1 The effect of metformin on kidney biochemical indexes and kidney pathological changes in HFD/STZ diabetic mice; AC observed the serum Cr, BUN and blood glucose levels of mice in the 24-week group after injection of STZ, and D.
Body weight of mice in the 24-week group after injection of STZ , E: Kidney weight/body weight ratio of mice in the 24-week group after STZ injection, F: FT 24-hour urine protein quantification of mice in the 24-hour group after STZ injection
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H&E(ac) and PAS(df) staining of kidney tissue sections (magnification×400), average ±SD, *P<0.

Figure 1 The effect of metformin on kidney biochemical indexes and kidney pathological changes in HFD/STZ diabetic mice; AC observed the serum Cr, BUN and blood glucose levels of mice in the 24-week group after injection of STZ, and D.

Figure 2 The effect of metformin on kidney oxidative stress and renal interstitial fibrosis in HFD/STZ diabetic mice; Group A 3 (magnification × 200) mouse kidney tissue 8-OHdG (magnification × 400, upper screen) and DHE AIHC analysis of staining (bottom screen)
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B, C, CBar images of 8-OHdG(B) and DHE(C) stained tissues, *P<0.

Figure 2 The effect of metformin on kidney oxidative stress and renal interstitial fibrosis in HFD/STZ diabetic mice; Group A 3 (magnification × 200) mouse kidney tissue 8-OHdG (magnification × 400, upper screen) and DHE AIHC analysis of staining (bottom screen)

Our results show for the first time that the AMPK agonist metformin activates mitosis by activating the p-AMPK-PINK1-Parkin pathway, thereby reducing renal oxidative stress and tubular interstitial fibrosis in HFD/STZ-induced diabetic mice

Han YC, Tang SQ, Liu YT,et al.

AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice.
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