Summary of project PR001653
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 PR001653. The data can be accessed directly via it's Project DOI: 10.21228/M81Q6Q This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001653 |
| Project DOI: | doi: 10.21228/M81Q6Q |
| Project Title: | Metabolomic profiling of PMM2-CDG zebrafish in presence and absence of epalrestat |
| Project Summary: | Abnormal polyol metabolism has been predominantly associated with diabetes, where excess glucose is converted to sorbitol by aldose reductase (AR). Recently, abnormal polyol metabolism has also been implicated in phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG), and epalrestat, an AR inhibitor, proposed as a potential therapy for this disorder. Given that the PMM enzyme is not closely connected to polyol metabolism, and, unlike in diabetes, PMM2-CDG does not present with hyperglycemia in blood, the increased polyol production, and the therapeutic mechanism of epalrestat in PMM2-CDG remained largely elusive. PMM2-CDG is caused by deficiency of the PMM enzyme and results in a depletion of mannose-1-P and guanosine diphosphate mannose (GDP-mannose), which is essential for glycosylation. Here, we show that apart from glycosylation abnormalities, PMM2 deficiency also leads to changes in intracellular glucose flux, which results in an increase in intracellular polyols. Targeting AR with epalrestat decreases polyol levels and increases GDP-mannose in vivo in pmm2 mutant zebrafish. |
| Institute: | Mayo Clinic |
| Last Name: | Radenkovic |
| First Name: | Silvia |
| Address: | 200 2nd Ave SW Rochester MN, USA |
| Email: | radenkovic.silvia@mayo.edu |
| Phone: | 507(77) 6-6107 |
| Funding Source: | NIH, KU Leuven |
| Publications: | Tracer metabolomics reveals the role of aldose reductase in glycosylation |
| Contributors: | Silvia Radenkovic, Anna N. Ligezka, Sneha S. Mokashi, Karen Driesen, Lynn Dukes-Rimsky, Graeme Preston, Luckio F. Owuocha, Leila Sabbagh, Jehan Mousa, Christina Lam, Andrew Edmondson, Austin Larson, Matthew Schultz, Pieter Vermeersch, David Cassiman, Peter Witters, Lesa J. Beamer, Tamas Kozicz, Heather Flanagan-Steet, Bart Ghesquière, Eva Morava |
Summary of all studies in project PR001653
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002561 | Metabolomic profiling of PMM2-CDG zebrafish in presence and absence of epalrestat | Danio rerio | Mayo Clinic | MS | 2023-07-18 | 1 | 92 | Uploaded data (4.1G)* |
| ST002562 | Metabolomic profiling of PMM2-CDG patient fibroblasts in presence and absence of epalrestat | Homo sapiens | Mayo Clinic | MS | 2023-07-18 | 1 | 88 | Uploaded data (4.4G)* |
| ST002563 | Metabolomic profiling of PMM2-CDG after siRNA mediated KD of AKR1b1 | Homo sapiens | Mayo Clinic | MS | 2023-07-18 | 1 | 80 | Uploaded data (3.6G)* |
| ST002564 | Metabolomic profiling of PMM2-CDG after siRNA mediated KD of AKR1b1 and neuraminidase treatment | Homo sapiens | Mayo Clinic | MS | 2023-08-18 | 1 | 16 | Uploaded data (600.6M)* |
| ST002565 | Metabolomic profiling of PMM2-CDG after siRNA mediated KD of AKR1b1 - 13C6 glucose and fructose study | Homo sapiens | Mayo Clinic | MS | 2023-07-18 | 1 | 24 | Uploaded data (1.2G)* |
| ST002566 | Metabolomic profiling of PMM2-CDG patient fibroblasts | Homo sapiens | Mayo Clinic | MS | 2023-07-19 | 1 | 72 | Uploaded data (5.2G)* |
| ST002575 | Metabolomic profiling of PMM2-CDG patient fibroblasts by GC/MS | Homo sapiens | Mayo Clinic | MS | 2023-07-18 | 1 | 99 | Uploaded data (49.2M)* |
