Exendin-4 Protects β-Cells From Interleukin-1β–Induced Apoptosis by Interfering With the c-Jun NH2-Terminal Kinase Pathway

• DOI: 10.2337/db07-1214
• Publication Date: 2008-02-06T02:36:56Z
• Authors: Mourad Ferdaoussi; Saida Abdelli; Jiang-Yan Yang; Marion Cornu; Guy Niederhauser; Dimitri Favre; Christian Widmann; Romano Regazzi; Bernard Thorens; Gérard Waeber; Amar Abderrahmani
• Keywords: IBMX; c-jun; Protein kinase R

The pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) generates pancreatic beta-cells apoptosis mainly through activation of the c-Jun NH(2)-terminal kinase (JNK) pathway. This study was designed to investigate whether long-acting agonist hormone glucagon-like peptide 1 (GLP-1) receptor exendin-4 (ex-4), which mediates protective effects against cytokine-induced beta-cell apoptosis, could interfere with JNK pathway.Isolated human, rat, and mouse islets rat insulin-secreting INS-1E cells were incubated ex-4 in presence or absence IL-1 beta. activity assessed by solid-phase assay quantification expression. Cell determined scoring displaying pycnotic nuclei.Ex-4 inhibited induction pathway elicited effect mimicked use cAMP-raising agents isobutylmethylxanthine forskolin required protein A. Inhibition IBMX concomitant a rise levels islet-brain (IB1), potent blocker stress-induced In fact, as well induced expression IB1 at promoter level cAMP response element binding transcription factor 1. Suppression RNA interference strategy impaired beta.The data establish requirement action highlight GLP-1 mimetics new inhibitors signaling cytokines.