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

• 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. © 2022 The Author(s)

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

liver

mass spectrometry

multi-tissue

pancreatic islets

prediabetes

proteomics

skeletal muscle

T2D

type 2 diabetes

visceral adipose tissue

cholesterol

glucagon

insulin

proteome

cross-sectional study

genetics

human

impaired glucose tolerance

metabolism

non insulin dependent diabetes mellitus

Cross-Sectional Studies

Diabetes Mellitus

Type 2

Humans

Metabolic Networks and Pathways

Prediabetic State

type 2 diabetes

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)