Abstract
Diabetic kidney disease is a serious complication of diabetes that can ultimately lead to end-stage renal disease. The pathogenesis of diabetic kidney disease is complex, and fundamental research is still required to provide a better understanding of the driving forces behind it. We report regional metabolic aberrations from an untargeted mass spectrometry imaging study of kidney tissue using an insulinopenic rat model of diabetes. Diabetes was induced by intravenous injection of streptozotocin, and kidneys were harvested 2 weeks thereafter. Imaging was performed using nanospray desorption electrospray ionization connected to a high-mass-resolving mass spectrometer. No histopathological changes were observed in the kidney sections; however, mass spectrometry imaging revealed a significant increase in several 18-carbon unsaturated non-esterified fatty acid species and monoacylglycerols. Notably, these 18-carbon acyl chains were also constituents of several increased diacylglycerol species. In addition, a number of short- and long-chain acylcarnitines were found to be accumulated while several amino acids were depleted. This study presents unique regional metabolic data indicating a dysregulated energy metabolism in renal mitochondria as an early response to streptozotocin-induced type I diabetes.Graphical abstract
Highlights
Diabetic kidney disease (DKD) is a common complication of diabetes that can lead to end-stage renal disease (ESRD)
While previous metabolomic studies focused on investigating chemical changes in tissue of diabetic kidney or DKD after > 16 weeks [13, 14], this study focuses on metabolic alterations that occur only 2 weeks after disease onset
More than 250 ion images of low molecular weight ions with unique chemical formulas were acquired from kidney tissue sections with nano-DESI mass spectrometry imaging (MSI)
Summary
Diabetic kidney disease (DKD) is a common complication of diabetes that can lead to end-stage renal disease (ESRD). ESRD is a fatal condition requiring dialysis and renal transplantation [1]. Parts of this work were presented at XIXth Euroanalysis 2017, Stockholm (Sweden) in August/September 2017, and have been awarded with an ABC Best Poster Award. Hilde-Marléne Bergman and Lina Lindfors contributed to this work. Metabolic profiling provides detailed analysis of small metabolites in a sample and can be used to understand altered metabolic pathways in disease states. Mass spectrometry (MS) is a common technique for metabolic profiling for both targeted and untargeted analyses [5]. The features of MS have been important in studies screening biofluids—for metabolites as biomarkers for diagnosis of DKD, as well as to predict progression to ESRD [6]
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