α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approach
IntroductionDiabetic nephropathy (DN), a major complication of diabetes, presents with poor clinical outcomes and affects patients throughout their lifetime. α-Methyltryptophan (α-MT) is a blocker of the amino acid transporter. SLC6A14 and also an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1).Me...
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Frontiers Media S.A.
2025-01-01
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| author | Aimin Cai Dingchao Shen Qiushuang Xiong Jie Ding Yang Ding Xinlu Lin Lijia Chen Qing Yao Qing Yao Guangyong Lin Ruijie Chen Vadivel Ganapathy Vadivel Ganapathy Longfa Kou |
| author_facet | Aimin Cai Dingchao Shen Qiushuang Xiong Jie Ding Yang Ding Xinlu Lin Lijia Chen Qing Yao Qing Yao Guangyong Lin Ruijie Chen Vadivel Ganapathy Vadivel Ganapathy Longfa Kou |
| author_sort | Aimin Cai |
| collection | DOAJ |
| description | IntroductionDiabetic nephropathy (DN), a major complication of diabetes, presents with poor clinical outcomes and affects patients throughout their lifetime. α-Methyltryptophan (α-MT) is a blocker of the amino acid transporter. SLC6A14 and also an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1).MethodsIn this study, we employed a nuclear magnetic resonance-based metabolomic approach to investigate the therapeutic effects of α-MT in a db/db mouse model of DN and explore the underlying molecular mechanisms.ResultsThe results of the study demonstrated that α-MT significantly reduced the urinary excretion of albumin and creatinine, improved kidney function, and decreased renal fibrosis in db/db mice. Metabolomic analyses of kidney tissues and urine samples indicated that db/db mice displayed increased activity of the enzyme IDO1, and alongside pronounced metabolic disturbances. These disturbances are chiefly characterized by alterations in amino acid metabolism, energy production pathways, membrane biochemical features, and nicotinamide metabolism, all of which have been implicated in mTOR signaling and apoptotic pathways.DiscussionAdministration of α-MT to db/db mice showed evidence of IDO1 inhibition and rectification of metabolic dysfunctions with concurrent suppression of mTOR signaling and apoptosis. These findings highlight the potential of α-MT as a promising therapeutic agent for diabetic nephropathy. |
| format | Article |
| id | doaj-art-af0af76a5f8f415d9ebde470ef636b3c |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-af0af76a5f8f415d9ebde470ef636b3c2025-01-20T07:20:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.14636731463673α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approachAimin Cai0Dingchao Shen1Qiushuang Xiong2Jie Ding3Yang Ding4Xinlu Lin5Lijia Chen6Qing Yao7Qing Yao8Guangyong Lin9Ruijie Chen10Vadivel Ganapathy11Vadivel Ganapathy12Longfa Kou13Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, United StatesWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaIntroductionDiabetic nephropathy (DN), a major complication of diabetes, presents with poor clinical outcomes and affects patients throughout their lifetime. α-Methyltryptophan (α-MT) is a blocker of the amino acid transporter. SLC6A14 and also an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1).MethodsIn this study, we employed a nuclear magnetic resonance-based metabolomic approach to investigate the therapeutic effects of α-MT in a db/db mouse model of DN and explore the underlying molecular mechanisms.ResultsThe results of the study demonstrated that α-MT significantly reduced the urinary excretion of albumin and creatinine, improved kidney function, and decreased renal fibrosis in db/db mice. Metabolomic analyses of kidney tissues and urine samples indicated that db/db mice displayed increased activity of the enzyme IDO1, and alongside pronounced metabolic disturbances. These disturbances are chiefly characterized by alterations in amino acid metabolism, energy production pathways, membrane biochemical features, and nicotinamide metabolism, all of which have been implicated in mTOR signaling and apoptotic pathways.DiscussionAdministration of α-MT to db/db mice showed evidence of IDO1 inhibition and rectification of metabolic dysfunctions with concurrent suppression of mTOR signaling and apoptosis. These findings highlight the potential of α-MT as a promising therapeutic agent for diabetic nephropathy.https://www.frontiersin.org/articles/10.3389/fphar.2024.1463673/fullα-methyltryptophandiabetic nephropathymTORapoptosismetabolomics |
| spellingShingle | Aimin Cai Dingchao Shen Qiushuang Xiong Jie Ding Yang Ding Xinlu Lin Lijia Chen Qing Yao Qing Yao Guangyong Lin Ruijie Chen Vadivel Ganapathy Vadivel Ganapathy Longfa Kou α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approach Frontiers in Pharmacology α-methyltryptophan diabetic nephropathy mTOR apoptosis metabolomics |
| title | α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approach |
| title_full | α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approach |
| title_fullStr | α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approach |
| title_full_unstemmed | α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approach |
| title_short | α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approach |
| title_sort | α methyltryptophan mediated protection against diabetic nephropathy in db db mice as studied with a metabolomics approach |
| topic | α-methyltryptophan diabetic nephropathy mTOR apoptosis metabolomics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1463673/full |
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