Premium
Oxygen metabolic competition in the lactic acidotic diabetic kidney: A point of no return?
Author(s) -
Laustsen Christoffer,
Lipsø Kasper,
Østergaard Jakob Appel,
Mose Per,
Flyvbjerg Allan,
Pedersen Michael,
Palm Fredrik,
ArdenkjaerLarsen Jan Henrik
Publication year - 2016
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.30.1_supplement.740.7
Subject(s) - medicine , endocrinology , lactic acidosis , hypoxia (environmental) , diabetes mellitus , diabetic nephropathy , acidosis , metabolic acidosis , oxygen , kidney , chemistry , organic chemistry
Diabetic nephropathy is directly related to renal hypoxia, with an increased mitochondrial uncoupling and increased energy demand to maintain normal renal function. Lowering the oxygen content in inspired air has shown to worsen the prognostic outcome of diabetic patients independent of glycemic control. We therefore tested the hypothesis that acutely altered renal oxygen availability alters metabolic pathways related to cellular energy production. Methods and materials Hyperpolarized 13 C‐MRI and blood oxygenation level‐dependent (BOLD) 1 H‐MRI were used to investigate the renal metabolic changes following acute changes in oxygen content in the inspired air in control and streptozotocin‐induced insulinopenic rats with and without insulin treatment. Results The severe lactic acidosis phenotype of diabetes, show a negative sensitivity towards oxygen changes, with a 12% and 16% reduction in the lactate‐to‐total carbon ratio change in both treated and untreated animals, however with no response differences between the treated and untreated group. Discussion The negative response to changes in oxygen availability can be the result of an increased lactate pool size masking the Pasteur effect, thus highlighting a key event in the development of kidney disease. The inability of insulin to normalize the lactate‐to‐pyruvate conversion in the present study indicates maintained elevated metabolic flux in these kidneys. Support or Funding Information The study was supported by The Simon Spies Foundation and the Danish National Research Foundation. Sascha Gude and Line Nielsen are acknowledged for their laboratory assistance.