Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes and normal tissues

View ORCID ProfileKlev Diamanti, View ORCID ProfileMarco Cavalli, View ORCID ProfileMaria J. Pereira, Gang Pan, Casimiro Castillejo-Lopez, Chanchal Kumar, Filip Mundt, View ORCID ProfileJan Komorowski, View ORCID ProfileAtul Shahaji Deshmukh, View ORCID ProfileMatthias Mann, View ORCID ProfileOlle Korsgren, View ORCID ProfileJan W. Eriksson, View ORCID ProfileClaes Wadelius
doi: https://doi.org/10.1101/2021.05.09.443296
Klev Diamanti
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Klev Diamanti
Marco Cavalli
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marco Cavalli
Maria J. Pereira
2Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Maria J. Pereira
Gang Pan
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Casimiro Castillejo-Lopez
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chanchal Kumar
3Translational Science & Experimental Medicine, Early Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
4Karolinska Institutet/AstraZeneca Integrated CardioMetabolic Center (KI/AZ ICMC), Department of Medicine, Novum, Huddinge, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Filip Mundt
5Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Denmark
6Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jan Komorowski
7Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
8Institute of Computer Science, Polish Academy of Sciences, Warsaw, Poland
9Washington National Primate Research Center, Seattle, WA, USA
10Swedish Collegium for Advanced Study, Uppsala, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jan Komorowski
Atul Shahaji Deshmukh
5Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Denmark
11Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Atul Shahaji Deshmukh
Matthias Mann
5Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Denmark
12Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Matthias Mann
Olle Korsgren
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
13Department of Medicine, University of Gothenburg, Gothenburg, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Olle Korsgren
Jan W. Eriksson
2Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jan W. Eriksson
Claes Wadelius
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Claes Wadelius
  • For correspondence: claes.wadelius@igp.uu.se
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Data/Code
  • Preview PDF
Loading

Abstract

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.

Competing Interest Statement

CK is an employee of AstraZeneca. JWE has received research grants and honoraria from AstraZeneca.

Footnotes

  • http://bioinf.icm.uu.se:3838/multitissue_ms_proteomics/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted May 10, 2021.
Download PDF

Supplementary Material

Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes and normal tissues
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes and normal tissues
Klev Diamanti, Marco Cavalli, Maria J. Pereira, Gang Pan, Casimiro Castillejo-Lopez, Chanchal Kumar, Filip Mundt, Jan Komorowski, Atul Shahaji Deshmukh, Matthias Mann, Olle Korsgren, Jan W. Eriksson, Claes Wadelius
bioRxiv 2021.05.09.443296; doi: https://doi.org/10.1101/2021.05.09.443296
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes and normal tissues
Klev Diamanti, Marco Cavalli, Maria J. Pereira, Gang Pan, Casimiro Castillejo-Lopez, Chanchal Kumar, Filip Mundt, Jan Komorowski, Atul Shahaji Deshmukh, Matthias Mann, Olle Korsgren, Jan W. Eriksson, Claes Wadelius
bioRxiv 2021.05.09.443296; doi: https://doi.org/10.1101/2021.05.09.443296

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4096)
  • Biochemistry (8801)
  • Bioengineering (6498)
  • Bioinformatics (23415)
  • Biophysics (11775)
  • Cancer Biology (9178)
  • Cell Biology (13304)
  • Clinical Trials (138)
  • Developmental Biology (7426)
  • Ecology (11394)
  • Epidemiology (2066)
  • Evolutionary Biology (15129)
  • Genetics (10421)
  • Genomics (14031)
  • Immunology (9157)
  • Microbiology (22136)
  • Molecular Biology (8802)
  • Neuroscience (47481)
  • Paleontology (350)
  • Pathology (1424)
  • Pharmacology and Toxicology (2487)
  • Physiology (3717)
  • Plant Biology (8074)
  • Scientific Communication and Education (1434)
  • Synthetic Biology (2220)
  • Systems Biology (6025)
  • Zoology (1251)