Impact of Diabetic Stress Conditions on Renal Cell Metabolome
Diabetic kidney disease is a major complication in diabetes mellitus, and the most common reason for end-stage renal disease. Patients suffering from diabetes mellitus encounter glomerular damage by basement membrane thickening, and develop albuminuria. Subsequently, albuminuria can deteriorate the...
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MDPI AG
2019-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/8/10/1141 |
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| author | Simon Lagies Roman Pichler Tillmann Bork Michael M. Kaminski Kevin Troendle Stefan Zimmermann Tobias B. Huber Gerd Walz Soeren S. Lienkamp Bernd Kammerer |
| author_facet | Simon Lagies Roman Pichler Tillmann Bork Michael M. Kaminski Kevin Troendle Stefan Zimmermann Tobias B. Huber Gerd Walz Soeren S. Lienkamp Bernd Kammerer |
| author_sort | Simon Lagies |
| collection | DOAJ |
| description | Diabetic kidney disease is a major complication in diabetes mellitus, and the most common reason for end-stage renal disease. Patients suffering from diabetes mellitus encounter glomerular damage by basement membrane thickening, and develop albuminuria. Subsequently, albuminuria can deteriorate the tubular function and impair the renal outcome. The impact of diabetic stress conditions on the metabolome was investigated by untargeted gas chromatography−mass spectrometry (GC-MS) analyses. The results were validated by qPCR analyses. In total, four cell lines were tested, representing the glomerulus, proximal nephron tubule, and collecting duct. Both murine and human cell lines were used. In podocytes, proximal tubular and collecting duct cells, high glucose concentrations led to global metabolic alterations in amino acid metabolism and the polyol pathway. Albumin overload led to the further activation of the latter pathway in human proximal tubular cells. In the proximal tubular cells, aldo-keto reductase was concordantly increased by glucose, and partially increased by albumin overload. Here, the combinatorial impact of two stressful agents in diabetes on the metabolome of kidney cells was investigated, revealing effects of glucose and albumin on polyol metabolism in human proximal tubular cells. This study shows the importance of including highly concentrated albumin in in vitro studies for mimicking diabetic kidney disease. |
| first_indexed | 2024-03-12T09:20:24Z |
| format | Article |
| id | doaj.art-a91776ebcf7c4988a28d0b99388a9ade |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T09:20:24Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a91776ebcf7c4988a28d0b99388a9ade2023-09-02T14:32:10ZengMDPI AGCells2073-44092019-09-01810114110.3390/cells8101141cells8101141Impact of Diabetic Stress Conditions on Renal Cell MetabolomeSimon Lagies0Roman Pichler1Tillmann Bork2Michael M. Kaminski3Kevin Troendle4Stefan Zimmermann5Tobias B. Huber6Gerd Walz7Soeren S. Lienkamp8Bernd Kammerer9Center for Biological Systems Analysis (ZBSA), Albert-Ludwigs-University Freiburg, Habsburgerstr. 49, 79104 Freiburg, GermanyDepartment of Medicine, Renal Division, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyDepartment of Medicine, Renal Division, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyDepartment of Medicine, Renal Division, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyLaboratory for MEMS Applications, IMTEK–Department of Microsystems Engineering, University of Freiburg, 79110 Freiburg, GermanyLaboratory for MEMS Applications, IMTEK–Department of Microsystems Engineering, University of Freiburg, 79110 Freiburg, GermanyIII. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Medicine, Renal Division, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyDepartment of Medicine, Renal Division, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyCenter for Biological Systems Analysis (ZBSA), Albert-Ludwigs-University Freiburg, Habsburgerstr. 49, 79104 Freiburg, GermanyDiabetic kidney disease is a major complication in diabetes mellitus, and the most common reason for end-stage renal disease. Patients suffering from diabetes mellitus encounter glomerular damage by basement membrane thickening, and develop albuminuria. Subsequently, albuminuria can deteriorate the tubular function and impair the renal outcome. The impact of diabetic stress conditions on the metabolome was investigated by untargeted gas chromatography−mass spectrometry (GC-MS) analyses. The results were validated by qPCR analyses. In total, four cell lines were tested, representing the glomerulus, proximal nephron tubule, and collecting duct. Both murine and human cell lines were used. In podocytes, proximal tubular and collecting duct cells, high glucose concentrations led to global metabolic alterations in amino acid metabolism and the polyol pathway. Albumin overload led to the further activation of the latter pathway in human proximal tubular cells. In the proximal tubular cells, aldo-keto reductase was concordantly increased by glucose, and partially increased by albumin overload. Here, the combinatorial impact of two stressful agents in diabetes on the metabolome of kidney cells was investigated, revealing effects of glucose and albumin on polyol metabolism in human proximal tubular cells. This study shows the importance of including highly concentrated albumin in in vitro studies for mimicking diabetic kidney disease.https://www.mdpi.com/2073-4409/8/10/1141diabetic kidney diseasemetabolomicsGC-MSdiabetic nephropathyalbumin stresstubulepodocytediabetic complicationpolyol metabolism |
| spellingShingle | Simon Lagies Roman Pichler Tillmann Bork Michael M. Kaminski Kevin Troendle Stefan Zimmermann Tobias B. Huber Gerd Walz Soeren S. Lienkamp Bernd Kammerer Impact of Diabetic Stress Conditions on Renal Cell Metabolome Cells diabetic kidney disease metabolomics GC-MS diabetic nephropathy albumin stress tubule podocyte diabetic complication polyol metabolism |
| title | Impact of Diabetic Stress Conditions on Renal Cell Metabolome |
| title_full | Impact of Diabetic Stress Conditions on Renal Cell Metabolome |
| title_fullStr | Impact of Diabetic Stress Conditions on Renal Cell Metabolome |
| title_full_unstemmed | Impact of Diabetic Stress Conditions on Renal Cell Metabolome |
| title_short | Impact of Diabetic Stress Conditions on Renal Cell Metabolome |
| title_sort | impact of diabetic stress conditions on renal cell metabolome |
| topic | diabetic kidney disease metabolomics GC-MS diabetic nephropathy albumin stress tubule podocyte diabetic complication polyol metabolism |
| url | https://www.mdpi.com/2073-4409/8/10/1141 |
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