Deletion of Uncoupling Protein-2 reduces renal mitochondrial leak respiration, intrarenal hypoxia and proteinuria in a mouse model of type 1 diabetes

Acta Physiologica
Malou Friederich-PerssonFredrik Palm

Abstract

Uncoupling protein-2 (UCP-2) can induce mitochondrial uncoupling in the diabetic kidney. Although mitochondrial uncoupling reduces oxidative stress originating from the mitochondria and can be regarded as a protective mechanism, the increased oxygen consumption occurring secondarily to increased mitochondria uncoupling, that is leak respiration, may contribute to kidney tissue hypoxia. Using UCP-2-/- mice, we tested the hypothesis that UCP-2-mediated leak respiration is important for the development of diabetes-induced intrarenal hypoxia and proteinuria. Kidney function, in vivo oxygen metabolism, urinary protein leakage and mitochondrial function were determined in wild-type and UCP-2-/- mice during normoglycaemia and 2 weeks after diabetes induction. Diabetic wild-type mice displayed mitochondrial leak respiration, pronounced intrarenal hypoxia, proteinuria and increased urinary KIM-1 excretion. However, diabetic UCP-2-/- mice did not develop increased mitochondrial leak respiration and presented with normal intrarenal oxygen levels, urinary protein and KIM-1 excretion. Although functioning as an antioxidant system, mitochondria uncoupling is always in co-occurrence with increased oxygen consumption, that is leak respiration;...Continue Reading

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Citations

Jan 7, 2020·American Journal of Physiology. Renal Physiology·Malou Friederich-Persson, Patrik Persson
Mar 17, 2020·Acta Physiologica·Isabel Auge
Jan 31, 2019·Scientific Reports·Lucy M HinderEva L Feldman
Dec 4, 2019·American Journal of Physiology. Renal Physiology·Aurélie EdwardsAnita T Layton
Feb 7, 2021·Nature Reviews. Nephrology·Holger ScholzPontus B Persson
Oct 17, 2020·Acta Physiologica·Ralf Mrowka

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