PXD027597

PXD027597 is an original dataset announced via ProteomeXchange.

Title	Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes and normal tissues
Description	Defects in pancreatic islets and the progression of multi-tissue insulin resistance in combination with environmental factors are the main causes of type 2 diabetes (T2D). Mass spectrometry-based proteomics of five key-metabolic tissues on a cohort of 42 multi-organ donors provided deep coverage of the proteomes of pancreatic islets, visceral adipose tissue (VAT), liver, skeletal muscle and serum. Enrichment analysis of gene ontology (GO) terms built a tissue-specific map of the chronological order of altered biological processes across healthy controls (CTRL), pre-diabetes (PD) and T2D subjects. This unique dataset allowed us to explore alterations of entire biological pathways and individual proteins in multiple tissues. We confirmed the significant decrease of the citric acid cycle and the respiratory electron transport in VAT and muscle of T2D and we provided a thorough visual representation of the complete set of downregulated proteins. Importantly, we found widespread novel alterations in relevant biological pathways including the increase in hemostasis in pancreatic islets of PD, the increase in the complement cascade in liver and pancreatic islets of PD and the elevation in cholesterol biosynthesis in liver of T2D. Overall, our findings suggest inflammatory, immune and vascular impairments in pancreatic islets as potentially causal factors of insufficient insulin production and increased glucagon levels in the early stages of T2D. In contrast alterations in lipid metabolism and mitochondrial function in the liver and VAT/muscle, respectively, became evident later in manifest T2D. This first multi-tissue proteomic map indicates the temporal order of tissue-specific metabolic dysregulation in T2D development.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:31:15.246.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Filip Mundt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-27 07:27:47	ID requested
1	2022-10-25 20:05:39	announced
2	2023-02-20 07:00:17	announced	2023-02-20: Updated project metadata.
⏵ 3	2023-11-14 08:31:17	announced	2023-11-14: Updated project metadata.

Diamanti K, Cavalli M, Pereira MJ, Pan G, Castillejo-L, ó, pez C, Kumar C, Mundt F, Komorowski J, Deshmukh AS, Mann M, Korsgren O, Eriksson JW, Wadelius C, Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes, and normal tissues. Cell Rep Med, 3(10):100763(2022) [pubmed]

submitter keyword: pancreatic islets,Proteomics, type 2 diabetes, serum, liver, skeletal muscle, visceral adipose tissue (VAT)

Matthias Mann
contact affiliation	Director of Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark and Director of Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Germany
contact email	mmann@biochem.mpg.de
lab head
Filip Mundt
contact affiliation	Novo Nordisk Foundation Center for Protein Research
contact email	filipmundt@gmail.com
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/2022/10/PXD027597

PRIDE project URI

• PRIDE
  1. PXD027597
     1. Label: PRIDE project
     2. Name: Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes and normal tissues