Summary of Study ST002403
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.
| Study ID | ST002403 |
| Study Title | Deep multi-omic profiling reveals extensive mitochondrial remodeling driven by glycemia in early diabetic kidney disease (Mitochondria) |
| Study Summary | Changes 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 transporter 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 | Baker Heart and Diabetes Institute |
| Laboratory | Metabolomics |
| Last Name | Huynh |
| First Name | Kevin |
| Address | 75 Commercial Road, Melbourne, 3004 |
| kevin.huynh@baker.edu.au | |
| Phone | 0385321537 |
| Submit Date | 2022-11-20 |
| Num Groups | 3 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-12-01 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Factors:
Subject type: Mammal; Subject species: Rattus norvegicus (Factor headings shown in green)
| mb_sample_id | local_sample_id | group | type |
|---|---|---|---|
| SA240108 | #739_mito | black | mito |
| SA240109 | #704_mito | black | mito |
| SA240110 | #730_mito | black | mito |
| SA240111 | #740_mito | black | mito |
| SA240112 | #753_mito | black | mito |
| SA240113 | #755_mito | black | mito |
| SA240114 | #754_mito | black | mito |
| SA240115 | #722_mito | black | mito |
| SA240116 | #734_mito | black | mito |
| SA240117 | #716_mito | black | mito |
| SA240118 | #710_mito | black | mito |
| SA240119 | #717_mito | black | mito |
| SA240120 | #712_mito | blue | mito |
| SA240121 | #748_mito | blue | mito |
| SA240122 | #714_mito | blue | mito |
| SA240123 | #749_mito | blue | mito |
| SA240124 | #737_mito | blue | mito |
| SA240125 | #744_mito | blue | mito |
| SA240126 | #725_mito | blue | mito |
| SA240127 | #720_mito | blue | mito |
| SA240128 | #752_mito | blue | mito |
| SA240129 | #713_mito | blue | mito |
| SA240130 | #724_mito | blue | mito |
| SA240131 | #711_mito | blue | mito |
| SA240132 | #701_mito | red | mito |
| SA240133 | #745_mito | red | mito |
| SA240134 | #733_mito | red | mito |
| SA240135 | #746_mito | red | mito |
| SA240136 | #719_mito | red | mito |
| SA240137 | #726_mito | red | mito |
| SA240138 | #723_mito | red | mito |
| SA240139 | #727_mito | red | mito |
| SA240140 | #728_mito | red | mito |
| SA240141 | #732_mito | red | mito |
| SA240142 | #731_mito | red | mito |
| SA240143 | #715_mito | red | mito |
| Showing results 1 to 36 of 36 |
