Summary of Study ST002562

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

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	ST002562
Study Title	Metabolomic profiling of PMM2-CDG patient fibroblasts in presence and absence of epalrestat
Study 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 both in vitro in patient-derived fibroblasts.
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
Submit Date	2023-04-14
Raw Data Available	Yes
Raw Data File Type(s)	mzML
Analysis Type Detail	LC-MS
Release Date	2023-07-18
Release Version	1

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Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id	local_sample_id	Genotype	Treatment
SA257743	SR50	PMM2-CDG	10microM epalrestat
SA257744	SR81	PMM2-CDG	10microM epalrestat
SA257745	SR49	PMM2-CDG	10microM epalrestat
SA257746	SR51	PMM2-CDG	10microM epalrestat
SA257747	SR20	PMM2-CDG	10microM epalrestat
SA257748	SR52	PMM2-CDG	10microM epalrestat
SA257749	SR01	PMM2-CDG	10microM epalrestat
SA257750	SR84	PMM2-CDG	10microM epalrestat
SA257751	SR35	PMM2-CDG	10microM epalrestat
SA257752	SR36	PMM2-CDG	10microM epalrestat
SA257753	SR34	PMM2-CDG	10microM epalrestat
SA257754	SR33	PMM2-CDG	10microM epalrestat
SA257755	SR83	PMM2-CDG	10microM epalrestat
SA257756	SR82	PMM2-CDG	10microM epalrestat
SA257757	SR19	PMM2-CDG	10microM epalrestat
SA257758	SR18	PMM2-CDG	10microM epalrestat
SA257759	SR67	PMM2-CDG	10microM epalrestat
SA257760	SR66	PMM2-CDG	10microM epalrestat
SA257761	SR04	PMM2-CDG	10microM epalrestat
SA257762	SR03	PMM2-CDG	10microM epalrestat
SA257763	SR02	PMM2-CDG	10microM epalrestat
SA257764	SR65	PMM2-CDG	10microM epalrestat
SA257765	SR68	PMM2-CDG	10microM epalrestat
SA257766	SR17	PMM2-CDG	10microM epalrestat
SA257767	SR71	PMM2-CDG	Vehicle
SA257768	SR72	PMM2-CDG	Vehicle
SA257769	SR54	PMM2-CDG	Vehicle
SA257770	SR70	PMM2-CDG	Vehicle
SA257771	SR53	PMM2-CDG	Vehicle
SA257772	SR69	PMM2-CDG	Vehicle
SA257773	SR55	PMM2-CDG	Vehicle
SA257774	SR38	PMM2-CDG	Vehicle
SA257775	SR40	PMM2-CDG	Vehicle
SA257776	SR39	PMM2-CDG	Vehicle
SA257777	SR56	PMM2-CDG	Vehicle
SA257778	SR37	PMM2-CDG	Vehicle
SA257779	SR86	PMM2-CDG	Vehicle
SA257780	SR21	PMM2-CDG	Vehicle
SA257781	SR22	PMM2-CDG	Vehicle
SA257782	SR23	PMM2-CDG	Vehicle
SA257783	SR88	PMM2-CDG	Vehicle
SA257784	SR08	PMM2-CDG	Vehicle
SA257785	SR05	PMM2-CDG	Vehicle
SA257786	SR06	PMM2-CDG	Vehicle
SA257787	SR07	PMM2-CDG	Vehicle
SA257788	SR24	PMM2-CDG	Vehicle
SA257789	SR87	PMM2-CDG	Vehicle
SA257790	SR85	PMM2-CDG	Vehicle
SA257791	SR75	WT	10microM epalrestat
SA257792	SR76	WT	10microM epalrestat
SA257793	SR28	WT	10microM epalrestat
SA257794	SR12	WT	10microM epalrestat
SA257795	SR25	WT	10microM epalrestat
SA257796	SR11	WT	10microM epalrestat
SA257797	SR42	WT	10microM epalrestat
SA257798	SR09	WT	10microM epalrestat
SA257799	SR10	WT	10microM epalrestat
SA257800	SR60	WT	10microM epalrestat
SA257801	SR59	WT	10microM epalrestat
SA257802	SR27	WT	10microM epalrestat
SA257803	SR26	WT	10microM epalrestat
SA257804	SR73	WT	10microM epalrestat
SA257805	SR44	WT	10microM epalrestat
SA257806	SR74	WT	10microM epalrestat
SA257807	SR58	WT	10microM epalrestat
SA257808	SR57	WT	10microM epalrestat
SA257809	SR43	WT	10microM epalrestat
SA257810	SR41	WT	10microM epalrestat
SA257811	SR78	WT	Vehicle
SA257812	SR79	WT	Vehicle
SA257813	SR80	WT	Vehicle
SA257814	SR77	WT	Vehicle
SA257815	SR45	WT	Vehicle
SA257816	SR29	WT	Vehicle
SA257817	SR30	WT	Vehicle
SA257818	SR16	WT	Vehicle
SA257819	SR15	WT	Vehicle
SA257820	SR13	WT	Vehicle
SA257821	SR14	WT	Vehicle
SA257822	SR31	WT	Vehicle
SA257823	SR32	WT	Vehicle
SA257824	SR62	WT	Vehicle
SA257825	SR63	WT	Vehicle
SA257826	SR61	WT	Vehicle
SA257827	SR48	WT	Vehicle
SA257828	SR46	WT	Vehicle
SA257829	SR47	WT	Vehicle
SA257830	SR64	WT	Vehicle

Showing results 1 to 88 of 88

Showing results 1 to 88 of 88