PXD054957-1

PXD054957 is an original dataset announced via ProteomeXchange.

Title	TSC22D1 is a newly identified inhibitor of insulinsecretion in pancreatic beta cells
Description	The loss of pancreatic beta cell function leads to chronically high blood glucose levels, contributing to diabetes mellitus, one of the leading causes of morbidity and mortality worldwide. Understanding the molecular mechanisms that regulate beta cell function could pave the way for the development of more effective anti-diabetic treatments. In this study, we identify the evolutionarily conserved TSC22D1 protein as a novel regulator of beta cell function. TSC22D1 depletion in INS-1E cells enhances the expression of beta cell identity genes, including Ins1, Ins2, Pdx1, Slc2a2, and Nkx6.1 and promotes glucose-stimulated insulin secretion without altering intracellular insulin content. Mechanistically, TSC22D1 and FoxO1 interact and regulate each other reciprocally to control beta cell function. Our follow-up interactome analysis revealed other novel proteins that differentially bind to TSC22D1 depending on glucose availability. These include several RNA-binding proteins such as Hnrnpm and Ddx46, as well as distinct tubulin isoforms, chaperones, and Scgn, a well-known regulator of insulin secretion. To further investigate the impact of TSC22D1 deficiency in cellular response to glucose stimulation, we performed RNA sequencing (RNA-Seq) experiment. The RNA-Seq results strongly aligned with our mass spectrometry interactome data and revealed mRNA processing, ribonucleoprotein complex biogenesis, and Golgi vesicle transport within the top pathways that are enriched upon glucose stimulation in TSC22D1 deficient cells. Overall, our study confirms that beta cell function requires tight regulation of insulin synthesis and secretion at multiple levels, even by a single protein, which we identified as TSC22D1, further highlighting the potential of targeting TSC22D1 in the development of new therapeutic strategies for diabetes.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-25_02:31:36.026.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ann-Christine König
SpeciesList	scientific name: Rattus rattus (Black rat); NCBI TaxID: 10117;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-16 04:43:08	ID requested
⏵ 1	2025-08-25 02:31:36	announced

10.1111/FEBS.70194;

submitter keyword: TSC22D1, FoxO1, Pancreatic Beta Cells and Insulin Secretion

Bilgen Ekim
contact affiliation	Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1 and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany.
contact email	Bilgen.Ekim@med.uni-heidelberg.de
lab head
Ann-Christine König
contact affiliation	HMGU Core Facility Proteomics
contact email	ann-christine.koenig@helmholtz-muenchen.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/08/PXD054957

PRIDE project URI

• PRIDE
  1. PXD054957
     1. Label: PRIDE project
     2. Name: TSC22D1 is a newly identified inhibitor of insulinsecretion in pancreatic beta cells