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.
| Study ID | ST002382 |
| Study Title | Deep multi-omic profiling reveals extensive mitochondrial remodeling driven by glycemia in early diabetic kidney disease |
| 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 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 Name | Caruana |
| First Name | Nikeisha |
| Address | 30 Flemington Rd, Parkville VIC 3052 |
| nikeisha.caruana@unimelb.edu.au | |
| Phone | 0383442219 |
| Submit Date | 2022-11-09 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-12-27 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN003881 |
|---|---|
| Analysis type | MS |
| Chromatography type | GC |
| Chromatography system | Shimadzu 2030 |
| Column | Agilent DB5-MS (30m x 0.25mm, 0.25um) |
| MS Type | ESI |
| MS instrument type | Triple quadrupole |
| MS instrument name | Shimazu TQ8040 |
| Ion Mode | UNSPECIFIED |
| Units | Peak area |
MS:
| MS ID: | MS003621 |
| Analysis ID: | AN003881 |
| Instrument Name: | Shimazu TQ8040 |
| Instrument Type: | Triple quadrupole |
| MS Type: | ESI |
| MS Comments: | The GC-MS system consisted of an AOC6000 autosampler, a 2030 Shimadzu gas chromatograph and a TQ8040 quadrupole mass spectrometer (Shimadzu, Japan), which was tuned according to the manufacturer’s recommendations using tris-(perfluorobutyl)-amine (CF43). GC-MS was performed on a 30 m Agilent DB-5 column with 1 µm film thickness and 0.25 mm internal diameter. The injection temperature (Inlet) and the MS transfer line were both set at 280°C and the ion source adjusted to 200°C. Helium was used as the carrier gas at a flow rate of 1 mL/min and argon gas was used as the collision cell gas to generate the multiple reaction monitoring (MRM) product ion. The analysis was performed under the following temperature program; start at injection 100°C, a hold for 4 minutes followed by a 10°C min-1 oven temperature ramp to 320°C followed by a final hold off of 11 minutes. Approximately 520 quantifying MRM targets were collected using Shimadzu Smart Database along with qualifier for each target, which covers about 350 endogenous metabolites and multiple 13C labelled internal standards. Both chromatograms and MRMs were evaluated using the Shimadzu GCMS browser and LabSolutions Insight software. |
| Ion Mode: | UNSPECIFIED |
