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Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with Losartan

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage kidney disease. Renin–angiotensin system inhibitors such as losartan are the predominant therapeutic options in clinical practice to treat DKD. Therefore, it is necessary to identify DKD-related metabolic prof...

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Autores principales: Hyeon, Jin Seong, Jung, Youngae, Lee, Gayoung, Ha, Hunjoo, Hwang, Geum-Sook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730544/
https://www.ncbi.nlm.nih.gov/pubmed/33255934
http://dx.doi.org/10.3390/ijms21238969
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author Hyeon, Jin Seong
Jung, Youngae
Lee, Gayoung
Ha, Hunjoo
Hwang, Geum-Sook
author_facet Hyeon, Jin Seong
Jung, Youngae
Lee, Gayoung
Ha, Hunjoo
Hwang, Geum-Sook
author_sort Hyeon, Jin Seong
collection PubMed
description Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage kidney disease. Renin–angiotensin system inhibitors such as losartan are the predominant therapeutic options in clinical practice to treat DKD. Therefore, it is necessary to identify DKD-related metabolic profiles that are affected by losartan. To investigate the change in metabolism associated with the development of DKD, we performed global and targeted metabolic profiling using 800 MHz nuclear magnetic resonance spectroscopy of urine samples from streptozotocin-induced diabetic mice (DM) with or without losartan administration. A principal component analysis plot showed that the metabolic pattern in the losartan-treated diabetic mice returned from that in the DM group toward that in the control mice (CM). We found that 33 urinary metabolites were significantly changed in DM compared with CM, and the levels of 16 metabolites among them, namely, glucose, mannose, myo-inositol, pyruvate, fumarate, 2-hydroxyglutarate, isobutyrate, glycine, threonine, dimethylglycine, methyldantoin, isoleucine, leucine, acetylcarnitine, 3-hydroxy-3-methylglutarate, and taurine, shifted closer to the control level in response to losartan treatment. Pathway analysis revealed that these metabolites were associated with branched-chain amino acid degradation; taurine and hypotaurine metabolism; glycine, serine, and threonine metabolism; the tricarboxylic acid cycle; and galactose metabolism. Our results demonstrate that metabolomic analysis is a useful tool for identifying the metabolic pathways related to the development of DKD affected by losartan administration and may contribute to the discovery of new therapeutic agents for DKD.
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spelling pubmed-77305442020-12-12 Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with Losartan Hyeon, Jin Seong Jung, Youngae Lee, Gayoung Ha, Hunjoo Hwang, Geum-Sook Int J Mol Sci Article Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage kidney disease. Renin–angiotensin system inhibitors such as losartan are the predominant therapeutic options in clinical practice to treat DKD. Therefore, it is necessary to identify DKD-related metabolic profiles that are affected by losartan. To investigate the change in metabolism associated with the development of DKD, we performed global and targeted metabolic profiling using 800 MHz nuclear magnetic resonance spectroscopy of urine samples from streptozotocin-induced diabetic mice (DM) with or without losartan administration. A principal component analysis plot showed that the metabolic pattern in the losartan-treated diabetic mice returned from that in the DM group toward that in the control mice (CM). We found that 33 urinary metabolites were significantly changed in DM compared with CM, and the levels of 16 metabolites among them, namely, glucose, mannose, myo-inositol, pyruvate, fumarate, 2-hydroxyglutarate, isobutyrate, glycine, threonine, dimethylglycine, methyldantoin, isoleucine, leucine, acetylcarnitine, 3-hydroxy-3-methylglutarate, and taurine, shifted closer to the control level in response to losartan treatment. Pathway analysis revealed that these metabolites were associated with branched-chain amino acid degradation; taurine and hypotaurine metabolism; glycine, serine, and threonine metabolism; the tricarboxylic acid cycle; and galactose metabolism. Our results demonstrate that metabolomic analysis is a useful tool for identifying the metabolic pathways related to the development of DKD affected by losartan administration and may contribute to the discovery of new therapeutic agents for DKD. MDPI 2020-11-26 /pmc/articles/PMC7730544/ /pubmed/33255934 http://dx.doi.org/10.3390/ijms21238969 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hyeon, Jin Seong
Jung, Youngae
Lee, Gayoung
Ha, Hunjoo
Hwang, Geum-Sook
Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with Losartan
title Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with Losartan
title_full Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with Losartan
title_fullStr Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with Losartan
title_full_unstemmed Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with Losartan
title_short Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with Losartan
title_sort urinary metabolomic profiling in streptozotocin-induced diabetic mice after treatment with losartan
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730544/
https://www.ncbi.nlm.nih.gov/pubmed/33255934
http://dx.doi.org/10.3390/ijms21238969
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