Growth arrest- and DNA-damage-inducible 45beta gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1beta-induced apoptosis in insulin-producing INS-1E cells

Claus Morten Larsen, M G Døssing, S Papa, G Franzoso, N Billestrup, Thomas Mandrup-Poulsen

30 Citations (Scopus)

Abstract

IL-1beta is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1beta activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen-activated protein kinase (MAPK) family. Inhibition of JNK prevents IL-1beta-mediated beta cell destruction. In mouse embryo fibroblasts and 3DO T cells, overexpression of the gene encoding growth arrest and DNA-damage-inducible 45beta (Gadd45b) downregulates pro-apoptotic JNK signalling. The aim of this study was to investigate if Gadd45b prevents IL-1beta-induced beta cell MAPK signalling and apoptosis.
Original languageEnglish
JournalDiabetologia
Volume49
Issue number5
Pages (from-to)980-9
Number of pages10
ISSN0012-186X
DOIs
Publication statusPublished - 1 May 2006

Keywords

  • 3T3 Cells
  • Animals
  • Antigens, Differentiation
  • Apoptosis
  • Cell Division
  • DNA Damage
  • DNA Primers
  • Extracellular Signal-Regulated MAP Kinases
  • Gene Expression Regulation, Neoplastic
  • Insulin
  • Insulinoma
  • Interleukin-1
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Pancreatic Neoplasms
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

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