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Mitochondrial Function and Superoxide Production is Reduced in the Diabetic Kidney and Restored by AMPK Activation
Author(s) -
You Young Hyun,
Dugan Laura L,
Naviaux Robert K,
Sharma Kumar
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.687.7
Subject(s) - superoxide , mitochondrial biogenesis , endocrinology , ampk , medicine , mitochondrion , chemistry , albuminuria , sod2 , kidney , biology , superoxide dismutase , biochemistry , phosphorylation , oxidative stress , protein kinase a , enzyme
Diabetic microvascular complications are considered to be mediated by a glucosedriven increase of mitochondrial superoxide anions. Here we report that superoxide production was reduced in the type 1 diabetic mouse kidney, as assessed by in vivo real‐time transcutaneous fluorescence, confocal microscopy and electron paramagnetic resonance analysis. Mitochondrial biogenesis was reduced with diabetes while pyruvate dehydrogenase (PDH) was phosphorylated, consistent with an overall reduction in mitochondrial glucose oxidation. Mitochondrial biogenesis, PDH activity and mitochondrial complex activity were rescued by the AMPK activator 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR ) in both the streptozotocin (STZ) and Akita ( Ins2 +/C96Y ) mouse models of type 1 diabetes. AICAR‐induced superoxide production in the diabetic kidney coincided with reduction of glomerular matrix and albuminuria. Furthermore, AMPKα2 −/− mice were found to have increased albuminuria and AMPK activity was reduced in human diabetic kidney disease. Taken together, the present results demonstrate that diabetic kidneys have reduced superoxide production, and AMPK activation enhances superoxide production and mitochondrial function while reducing disease activity. This study was supported by grants from the JDRF (KS and LLD) and the NIH for these studies (U01DK076133 KS, R01DK053867 KS, AG 030320 LLD).