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Diabetes‐induced up‐regulation of mitochondrial uncoupling protein‐2 (UCP‐2) results in increased ouabain‐insensitive oxygen consumption (Q O2 ) by renal proximal tubular (PT) cells
Author(s) -
Friederich Malou,
Fasching Angelica,
Liss Per,
Hansell Peter,
Palm Fredrik
Publication year - 2007
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.21.5.a453-b
Subject(s) - ouabain , medicine , endocrinology , mitochondrion , chemistry , renal cortex , streptozotocin , diabetes mellitus , superoxide , uncoupling protein , kidney , insulin , oxygen , biology , biochemistry , sodium , adipose tissue , enzyme , organic chemistry , brown adipose tissue
Up‐regulation of mitochondrial UCP‐2 provides the cell with a mechanism to counteract hyperglycemia‐induced formation of superoxide radicals. A potential devastating side‐effect of increased mitochondrial uncoupling is increased Q O2 to sustain ATP production leading to reduced tissue oxygen availability. We studied if the diabetes‐induced increase in Q O2 is linked to elevated UCP‐2‐levels in the kidney cortex of streptozotocin‐diabetic rats. UCP‐2 in kidney cortex (Western Blot) and Q O2 measured in vitro on isolated PT cells from controls (n=5), diabetics (n=5) and diabetic rats given insulin that reversed the hyperglycemia (n=7). Ouabain was used to inhibit transport‐related Q O2 , which was calculated as total Q O2 ‐ ouabain‐insensitive Q O2 . UCP‐2 increased 4.8‐fold in diabetic rats compared to controls (5.9±0.8 vs 1.2±0.4), with concomitant increase in ouabain‐insensitive Q O2 (19.4±1.8 vs 9.7±1.6 nmol·mg protein −1 ·min −1 ). Insulin treatment prevented the increases in UCP‐2 expression and ouabain‐insensitive Q O2 (1.1±0.1 and 11.4±1.3 nmol·mg protein −1 ·min −1 ). All groups had similar transport‐related Q O2 . In conclusion, diabetic rats have increased mitochondrial UCP‐2 expression in the kidney cortex and increased ouabain‐insensitive Q O2 , indicating increased mitochondrial uncoupling. The results points to a mitochondrial protective mechanism against hyperglycemia‐induced superoxide formation.