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

https://doi.org/10.1016/j.xcrm.2022.100763Get rights and content
Under a Creative Commons license
open access

Highlights

  • Mass spectrometry proteomics of 5 key metabolic tissues from 43 multi-organ donors

  • The study provides a map of tissue-specific metabolic dysregulations in PD and T2D

  • Inflammatory, immune, and vascular processes are altered in pancreatic islets in PD

  • Lipid and mitochondrial pathways are dysregulated in liver and VAT/muscle in T2D

Summary

Environmental and genetic factors cause defects in pancreatic islets driving type 2 diabetes (T2D) together with the progression of multi-tissue insulin resistance. Mass spectrometry proteomics on samples from five key metabolic tissues of a cross-sectional cohort of 43 multi-organ donors provides deep coverage of their proteomes. Enrichment analysis of Gene Ontology terms provides a tissue-specific map of altered biological processes across healthy, prediabetes (PD), and T2D subjects. We find widespread alterations in several relevant biological pathways, including increase in hemostasis in pancreatic islets of PD, increase in the complement cascade in liver and pancreatic islets of PD, and elevation in cholesterol biosynthesis in liver of T2D. Our findings point to inflammatory, immune, and vascular alterations in pancreatic islets in PD that are hypotheses to be tested for potential contributions to hormonal perturbations such as impaired insulin and increased glucagon production. This multi-tissue proteomic map suggests tissue-specific metabolic dysregulations in T2D.

Keywords

type 2 diabetes
T2D
prediabetes
multi-tissue
pancreatic islets
visceral adipose tissue
skeletal muscle
liver
mass spectrometry
proteomics

Data and code availability

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository under the accession number PRIDE: PXD027597.62 This data will be publicly available at the date of publication. Accession numbers are listed in the key resources table. Clinical data is provided in supplementary tables.

The pipeline for the analysis is available on GitHub https://github.com/klevdiamanti/multitissue_ms_proteomics. A web-based tool that allows visualization and exploration for levels of proteins across tissues is available on http://bioinf.icm.uu.se:3838/multitissue_ms_proteomics/. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

14

Present address: Translational and Disease Understanding, Research and Development, Grünenthal Ltd, Stokenchurch, UK

15

Lead contact