Summary of Study ST002382

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001532. The data can be accessed directly via it's Project DOI: 10.21228/M8P11T This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002382
Study TitleDeep multi-omic profiling reveals extensive mitochondrial remodeling driven by glycemia in early diabetic kidney disease
Study SummaryChanges in mitochondrial energy metabolism are thought to be central to the development of diabetic kidney disease (DKD); however, whether this response is explicitly driven by systemic glucose concentrations remains unknown. Here, we show that titrating blood glucose concentrations in vivo directly impacts mitochondrial morphology and bioenergetics and remodels the mitochondrial proteome in the kidney in early DKD. Mitoproteomic analysis revealed profound metabolic disturbances induced by severe hyperglycemia, including upregulation of enzymes involved in the TCA cycle and fatty acid metabolism, enhanced ketogenesis as well as extensive dysregulation of the mitochondrial SLC25 carrier family. The metabolite and lipid landscape were perturbed by severe hyperglycemia; untargeted metabolomics and lipidomics confirmed the enrichment of TCA cycle metabolites, an increase in triglyceride concentrations, and extensive and specific cardiolipin remodeling. Lowering blood glucose to moderate hyperglycemia stabilized all three omic landscapes, partially prevented changes in mitochondrial morphology and bioenergetics, and improved kidney injury. This study provides insights into altered substrate utilization and energy generation in the kidney early in diabetes, during moderate and severe hyperglycemia and has implications for therapeutic strategies aiming at the reinvigoration of mitochondrial function and signaling in diabetes.
Institute
University of Melbourne
Last NameCaruana
First NameNikeisha
Address30 Flemington Rd, Parkville VIC 3052
Emailnikeisha.caruana@unimelb.edu.au
Phone0383442219
Submit Date2022-11-09
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2022-12-27
Release Version1
Nikeisha Caruana Nikeisha Caruana
https://dx.doi.org/10.21228/M8P11T
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Mammal; Subject species: Rattus norvegicus (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA237835UNK-0046_6blank
SA237836UNK-0035_5blank
SA237837UNK-0024_4blank
SA237838UNK-0053_7blank
SA237839UNK-0054_8blank
SA237840UNK-0054_2blank
SA237841UNK-0053_9blank
SA237842UNK-0013_3blank
SA237783CG_740CTRL
SA237784CG_739CTRL
SA237785CG_734CTRL
SA237786CG_753CTRL
SA237787CGrerun_754CTRL
SA237788CG_755CTRL
SA237789CGrerun_755CTRL
SA237790CG_754CTRL
SA237791CG_722CTRL
SA237792CG_730CTRL
SA237793CG_710CTRL
SA237794CG_704CTRL
SA237795CG_717CTRL
SA237796CG_716CTRL
SA237797CG_749MHG
SA237798CG_748MHG
SA237799CG_725MHG
SA237800CG_714MHG
SA237801CGrerun_752MHG
SA237802CG_752MHG
SA237803CG_711MHG
SA237804CG_712MHG
SA237805CG_713MHG
SA237806CG_720MHG
SA237807CG_744MHG
SA237808CG_737MHG
SA237809CG_724MHG
SA237810UNK-0047_rerunQC
SA237811UNK-0041QC
SA237812UNK-0052_rerunQC
SA237813UNK-0052QC
SA237814UNK-0003QC
SA237815UNK-0047QC
SA237816UNK-0030QC
SA237817UNK-0019QC
SA237818UNK-0014QC
SA237819UNK-0008QC
SA237820UNK-0025QC
SA237821UNK-0036QC
SA237822CG_746SHG
SA237823CG_728SHG
SA237824CG_731SHG
SA237825CG_732SHG
SA237826CG_733SHG
SA237827CG_727SHG
SA237828CG_726SHG
SA237829CG_715SHG
SA237830CG_719SHG
SA237831CG_723SHG
SA237832CG_745SHG
SA237833CGrerun_746SHG
SA237834CG_701SHG
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