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Hyperpolarized 13 C MRS reveals hypoxia accelerates pseudo hypoxia in the diabetic kidney (890.8)
Author(s) -
Laustsen Christoffer,
Lycke Sara,
Palm Fredrik,
Østergaard Jakob,
Bibby Bo,
Nørregaard Rikke,
Flyvbjerg Allan,
Pedersen Michael,
ArdenkjærLarsen Jan
Publication year - 2014
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.28.1_supplement.890.8
Subject(s) - medicine , endocrinology , pyruvate dehydrogenase complex , lactate dehydrogenase , hypoxia (environmental) , pyruvate dehydrogenase kinase , nicotinamide adenine dinucleotide phosphate , chemistry , kidney , glycolysis , nicotinamide adenine dinucleotide , dehydrogenase , diabetic nephropathy , oxygen , metabolism , biochemistry , nad+ kinase , enzyme , organic chemistry , oxidase test
In diabetic patients, reduced renal oxygen availability is associated with a higher risk of diabetic nephropathy (DN) [1]. Recently, dynamic nuclear polarization hyperpolarized [1‐13C]pyruvate has shown an increased lactate conversion (lactate dehydrogenase activity) in the diabetic kidney, as a consequence of increased nicotinamide adenine dinucleotide (NADH) substrate generated by glucose‐mediated elevated flux through the polyol pathway, while the pyruvate dehydrogenase activity (PDH) is unaltered (pseudo hypoxia) [2]. In this study, we evaluated the renal oxygenation level and energy metabolism in diabetes‐suffering rats in response to altered oxygen availability, using blood oxygen level dependent (BOLD) MRI and hyperpolarized [1‐13C]pyruvate MRI, in response to hypoxic, normoxic and hyperoxic conditions. Specifically, we investigated the enzymatic activity of lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and pyruvate dehydrogenase (PDH). We show that reduced oxygen availability in the diabetic kidney alters the energy metabolism of pyruvate by increasing the lactate and alanine formation from pyruvate despite intact oxidative phosphorylation. Grant Funding Source : Supported by The Simon Spies Foundation, The Danish Kidney Foundation, Helen and Ejnar Bjørnows Foun