Urinary 2-Hydroxyglutarate Enantiomers Are Markedly Elevated in a Murine Model of Type 2 Diabetic Kidney Disease.

ABSTRACT: Metabolic reprogramming is a hallmark of diabetic kidney disease (DKD); nutrient overload leads to increased production of metabolic byproducts that may become toxic at high levels. One metabolic byproduct may be 2-hydroxyglutarate (2-HG), a metabolite with many regulatory functions that exists in both enantiomeric forms physiologically. We quantitatively determined the levels of L and D-2HG enantiomers in the urine, plasma, and kidney cortex of db/db mice, a pathophysiologically relevant murine model of type 2 diabetes and DKD. We found increased fractional excretion of both L and D-2HG enantiomers, suggesting increased tubular secretion and/or production of the two metabolites in DKD. Quantitation of TCA cycle metabolites in db/db cortex suggests that TCA cycl

SUBMITTER: Baek J 

PROVIDER: S-EPMC8400583 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature