PXD074720

PXD074720 is an original dataset announced via ProteomeXchange.

Title	The type 1 diabetes (T1D) susceptibility gene PGM1 disrupts metabolic homeostasis in pancreatic beta cell in response to viral triggers: A new genetic-environmental mechanism in T1D
Description	PGM1 is a type 1 diabetes (T1D) susceptibility gene that potentially plays a key role in regulating central carbon metabolism in -cells. Previous work suggested that -cell PGM1 transcription is lowered after Coxsackie B4 infection. Thus, we hypothesized that in response to viral triggers, decreased PGM1 levels could disrupt beta cell metabolic homeostasis which may lead to β-cell fragility and T1D. First, we have shown that the synthetic double stranded viral analogue Poly I:C attenuated PGM1 transcription both in human islets and EndoC-BH1 human β-cell line. PGM1 deficiency in EndoC-BH1 cells drastically enhanced the metabolic flux to glycolysis, TCA, pentose phosphate pathway, and hexosamine biosynthetic pathway, but the flux to serine/glycine biosynthesis was attenuated. Moreover, autophagic flux, which is dependent on the lysosomal glycosylated protein function, was significantly impaired in PGM1 deficient cells. The disruption of metabolic homeostasis resulted in the induction of adaptive response to stress, including upregulation of ATF3 and CHOP mRNA expression. In addition, PGM1 deficiency potentiated IL-1, TNF-, IFN- induced apoptosis. These results suggest that PGM1 deficiency upon viral infection predisposes -cells to metabolic imbalance and that phosphoglucomutase 1 could be a metabolic target that lowers -cell fragility in the presence of diabetogenic stimuli.
HostingRepository	PRIDE
AnnounceDate	2026-02-22
AnnouncementXML	Submission_2026-02-21_18:51:07.124.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simone Sidoli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-21 18:24:53	ID requested
⏵ 1	2026-02-21 18:51:07	announced

Dataset with its publication pending

submitter keyword: T1D,PGM1

Simone Sidoli
contact affiliation	Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States
contact email	simone.sidoli@einsteinmed.edu
lab head
Simone Sidoli
contact affiliation	Albert Einstein College of Medicine
contact email	simone.sidoli@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD074720
     1. Label: PRIDE project
     2. Name: The type 1 diabetes (T1D) susceptibility gene PGM1 disrupts metabolic homeostasis in pancreatic beta cell in response to viral triggers: A new genetic-environmental mechanism in T1D