Impact of Diabetic Stress Conditions on Renal Cell Metabolome

Cells

Bernd Kammerer¹  Simon Lagies¹  Tillmann Bork²  SoerenS. Lienkamp²  Roman Pichler²  MichaelM. Kaminski²  Gerd Walz²  TobiasB. Huber³  Stefan Zimmermann⁴  Kevin Troendle⁴ 

[1] Center for Biological Systems Analysis (ZBSA), Albert-Ludwigs-University Freiburg, Habsburgerstr. 49, 79104 Freiburg, Germany;Department of Medicine, Renal Division, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany;III. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;Laboratory for MEMS Applications, IMTEK–Department of Microsystems Engineering, University of Freiburg, 79110 Freiburg, Germany;

关键词: diabetic kidney disease;    metabolomics;    GC-MS;    diabetic nephropathy;    albumin stress;    tubule;    podocyte;    diabetic complication;    polyol metabolism;   

DOI  :  10.3390/cells8101141

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown