Journal
JOURNAL OF PROTEOME RESEARCH
Volume 12, Issue 9, Pages 4193-4206Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr400527q
Keywords
GLP-1; Type 1 diabetes; human islets; cytokines; 2D-DIGE; protein interaction networks
Categories
Funding
- European Community [241447]
- KU Leuven (Geconcerteerde Onderzoeksactie) [GOA 12/24]
- Flemish Research Foundation [FWO G.0649.08, G.0619.12]
- Juvenile Diabetes Research Foundation International [17-2012-129]
- Interuniversity Attraction Poles Program-Belgian Federal Science Policy [P7/13]
Ask authors/readers for more resources
Glucagon-like peptide-1 (GLP-1) has been shown to protect pancreatic beta-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-1 beta and IFN-gamma) 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 beta-cell protection. Co-incubation of cytokine-treated human islets with GLP-1 resulted in a marked protection of beta-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available