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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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/8969 |
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| author | Jin Seong Hyeon Youngae Jung Gayoung Lee Hunjoo Ha Geum-Sook Hwang |
| author_facet | Jin Seong Hyeon Youngae Jung Gayoung Lee Hunjoo Ha Geum-Sook Hwang |
| author_sort | Jin Seong Hyeon |
| collection | DOAJ |
| 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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| id | doaj.art-ad18c466332e4b6b87e002d7846987ad |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:33:14Z |
| publishDate | 2020-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ad18c466332e4b6b87e002d7846987ad2023-11-20T22:23:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123896910.3390/ijms21238969Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with LosartanJin Seong Hyeon0Youngae Jung1Gayoung Lee2Hunjoo Ha3Geum-Sook Hwang4Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, KoreaIntegrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, KoreaGraduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, KoreaGraduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, KoreaIntegrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, KoreaDiabetic 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.https://www.mdpi.com/1422-0067/21/23/8969metabolomicsdiabetic kidney diseaselosartanNMR |
| spellingShingle | Jin Seong Hyeon Youngae Jung Gayoung Lee Hunjoo Ha Geum-Sook Hwang Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with Losartan International Journal of Molecular Sciences metabolomics diabetic kidney disease losartan NMR |
| 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 | metabolomics diabetic kidney disease losartan NMR |
| url | https://www.mdpi.com/1422-0067/21/23/8969 |
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