Glucagon-like peptide-1 protects human islets against cytokine-mediated β-cell dysfunction and death: a proteomic study of the pathways involved.
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.
Laboratory for Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Dieter
D
Rondas
Marco
M
Bugliani
Wannes
W
D'Hertog
Kasper
K
Lage
Mathilde
M
Masini
Etienne
E
Waelkens
Piero
P
Marchetti
Chantal
C
Mathieu
Lut
L
Overbergh
D000328:Adult; D000368:Aged; D017209:Apoptosis; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007371:Interferon-gamma / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology; D007515:Islets of Langerhans / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D060066:Protein Interaction Maps; D059748:Proteolysis; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D012343:RNA, Transfer / Q000096:biosynthesis; D022142:Secretory Vesicles / Q000378:metabolism
D007328:Insulin; D053583:Interleukin-1beta; D020543:Proteome; D007371:Interferon-gamma; D052216:Glucagon-Like Peptide 1; D012343:RNA, Transfer