Glucagon-like peptide-1 protects human islets against cytokine-mediated β-cell dysfunction and death: a proteomic study of the pathways involved

J Proteome Res. 2013 Sep 6;12(9):4193-206. doi: 10.1021/pr400527q. Epub 2013 Aug 26.


Glucagon-like peptide-1 (GLP-1) has been shown to protect pancreatic β-cells against cytokine-induced dysfunction and destruction. The mechanisms through which GLP-1 exerts its effects are complex and still poorly understood. The aim of this study was to analyze the protein expression profiles of human islets of Langerhans treated with cytokines (IL-1β and IFN-γ) in the presence or absence of GLP-1 by 2D difference gel electrophoresis and subsequent protein interaction network analysis to understand the molecular pathways involved in GLP-1-mediated β-cell protection. Co-incubation of cytokine-treated human islets with GLP-1 resulted in a marked protection of β-cells against cytokine-induced apoptosis and significantly attenuated cytokine-mediated inhibition of glucose-stimulated insulin secretion. The cytoprotective effects of GLP-1 coincided with substantial alterations in the protein expression profile of cytokine-treated human islets, illustrating a counteracting effect on proteins from different functional classes such as actin cytoskeleton, chaperones, metabolic proteins, and islet regenerating proteins. In summary, GLP-1 alters in an integrated manner protein networks in cytokine-exposed human islets while protecting them against cytokine-mediated cell death and dysfunction. These data illustrate the beneficial effects of GLP-1 on human islets under immune attack, leading to a better understanding of the underlying mechanisms involved, a prerequisite for improving therapies for diabetic patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis*
  • Cells, Cultured
  • Cytoskeleton / metabolism
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Female
  • Glucagon-Like Peptide 1 / physiology*
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Interferon-gamma / physiology
  • Interleukin-1beta / physiology
  • Islets of Langerhans / pathology
  • Islets of Langerhans / physiopathology
  • Male
  • Middle Aged
  • Protein Interaction Maps
  • Proteolysis
  • Proteome / metabolism
  • Proteomics
  • RNA, Transfer / biosynthesis
  • Secretory Vesicles / metabolism


  • Insulin
  • Interleukin-1beta
  • Proteome
  • Interferon-gamma
  • Glucagon-Like Peptide 1
  • RNA, Transfer