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Metabolic changes in urine and serum during progression of diabetic kidney disease in a mouse model

  • 주제(키워드) Diabetic kidney disease , Metabolite profiling , db/db mice , NMR , Progression
  • 주제(기타) Biochemistry & Molecular Biology; Biophysics
  • 설명문(일반) [Kim, Nan Hee; Kim, Nam Hoon] Korea Univ, Coll Med, Dept Internal Med, Div Endocrinol & Metab, Seoul, South Korea; [Hyeon, Jin Seong; Jang, Seo Young; Hwang, Geum Sook] Korea Basic Sci Inst, Western Seoul Ctr, Integrated Metabol Res Grp, Seoul, South Korea; [Hyeon, Jin Seong; Cho, Ahreum; Lee, Gayoung; Ha, Hunjoo] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul, South Korea; [Jang, Seo Young; Ha, Hunjoo; Hwang, Geum Sook] Ewha Womans Univ, Dept Chem & Nano Sci, Seoul, South Korea; [Kim, Mi-Kyung] Keimyung Univ, Dongsan Med Ctr, Dept Internal Med, Div Endocrinol & Metab, Daegu, South Korea; [Lee, Eun Young] Soonchunhyang Univ, Cheonan Hosp, Dept Internal Med, Div Nephrol, Cheonan, South Korea; [Chung, Choon Hee] Yonsei Univ, Wonju Coll Med, Div Endocrinol & Metab, Dept Internal Med, Wonju, South Korea
  • 등재 SCIE, SCOPUS
  • 발행기관 ELSEVIER SCIENCE INC
  • 발행년도 2018
  • URI http://www.dcollection.net/handler/ewha/000000151550
  • 본문언어 영어
  • Published As http://dx.doi.org/10.1016/j.abb.2018.03.042

초록/요약

Diabetic kidney disease (DKD) involves various pathogenic processes during progression to end stage renal disease, and activated metabolic pathways might be changing based on major pathophysiologic mechanisms as DKD progresses. In this study, nuclear magnetic resonance spectroscopy (NMR)-based metabolic profiling was performed in db/db mice to suggest potential biomarkers for early detection and its progression. We compared concentrations of serum and urinary metabolites between db/m and db/db mice at 8 or 20 weeks of age and investigated whether changes between 8 and 20 weeks in each group were significant. The metabolic profiles demonstrated significantly increased urine levels of glucose and tricarboxylic acid cycle intermediates at both 8 and 20 weeks of age in db/db mice. These intermediates also exhibited strong positive associations with urinary albumin excretion, suggesting that they may be potential biomarkers for early diagnosis. On the contrary, branched chain amino acid and homocysteine-methionine metabolism were activated early in the disease, whereas ketone and fatty acid metabolism were significantly changed in the late phase of the disease. We demonstrated phase-specific alterations in metabolites during progression of DKD. This study provides insights into perturbed mechanisms during evolution of the disease and identifies potential novel biomarkers for DKD.

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