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Comprehensive Proteomics Analysis of Stressed Human Islets Identifies GDF15 as a Target for Type 1 Diabetes

Ernesto S Nakayasu1, Farooq Syed2, Sarah A Tersey2

  • 1Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.

Cell Metabolism
|January 14, 2020
PubMed

Insights

Growth/differentiation factor 15 (GDF15) protects against inflammation-induced beta cell death in type 1 diabetes (T1D). Supplementing GDF15 reduced T1D incidence in mice, identifying it as a potential therapeutic target.

Area of Science:

  • Immunology
  • Endocrinology
  • Proteomics

Background:

  • Type 1 diabetes (T1D) involves progressive loss of pancreatic beta cells due to inflammatory cytokine signaling.
  • This signaling disrupts the balance of apoptosis-related proteins within beta cells.

Purpose of the Study:

  • To identify proteins regulated by inflammatory cytokines in human pancreatic islets.
  • To investigate the role of growth/differentiation factor 15 (GDF15) in T1D pathogenesis and its therapeutic potential.

Main Methods:

  • Comprehensive proteomics analysis of human pancreatic islets treated with interleukin-1β and interferon-γ.
  • Functional assays to assess the impact of GDF15 on apoptosis and in vivo efficacy in a mouse model of T1D.

Main Results:

  • Proteomics identified 387 significantly regulated proteins, including repressed GDF15.
  • GDF15 translation was blocked during inflammation and GDF15 was depleted in T1D islets.
  • Exogenous GDF15 inhibited cytokine-induced apoptosis in human islets and reduced diabetes incidence by 53% in NOD mice.

Conclusions:

  • Cytokine-regulated protein networks in human islets were identified.
  • GDF15 is a key protective factor against beta cell apoptosis in T1D and a promising therapeutic target.
Keywords:
GDF15apoptosiscytokinehuman isletsislet protective factorproteomicstype 1 diabetes

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