PGC1α Activators Mitigate Diabetic Tubulopathy by Improving Mitochondrial Dynamics and Quality Control

Figure 6

AICAR and metformin increase PGC1α expression and ameliorate albuminuria and renal morphologic characteristics in kidneys of streptozotocin- (STZ-) induced diabetic mice. (a and b) The STZ-induced diabetes group had higher blood glucose levels and reduced body weights compared with the normal control group. (c) The STZ-induced diabetic mice treated with AICAR or metformin exhibited a significant reduction in urine albumin excretion rate (UAER). (d and e) Tubular dilatation (asterisk) and tubular epithelial disruption (arrow) were observed in the diabetic control group. Treatment of STZ-induced diabetic mice with AICAR or metformin resulted in less cellular disruption. (f and g) Representative photographs of Masson’s trichrome-stained kidneys showed decreased renal fibrotic lesions in both AICAR and metformin-treated groups compared with the diabetic control group. (h and i) Restored PGC1α activity was confirmed by immunofluorescence and immunoblot analysis in diabetic kidneys treated with AICAR or metformin ( versus normal; versus diabetic control; scale bar 10 μm).

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