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Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells

Published inThe Journal of biological chemistry, vol. 280, no. 34, p. 30630-30637
Publication date2005
Abstract

Laminin-5-rich extracellular matrix derived from 804G cells (804G-ECM) engages beta1 integrins to induce spreading, improve glucose-stimulated insulin secretion (GSIS), and increase survival of pancreatic beta cells. The present study examines whether 804G-ECM activates the transcriptional activity of NF-kappaB and the involvement of NF-kappaB in those effects of 804G-ECM on pancreatic beta cells. 804G-ECM induces nuclear translocation and the DNA binding activity of the p65 subunit of NF-kappaB. 804G-ECM-induced nuclear translocation of NF-kappaB was weak as compared with that induced by interleukin-1beta. Transient 804G-ECM-induced DNA binding activity of NF-kappaB (peak at 2 h) and overexpression of NF-kappaB target genes IkappaB alpha and NF-kappaB1(p105) (peak at 4 h) were observed. When NF-kappaB was inhibited by an inhibitor of IkappaB alpha phosphorylation (Bay 11-7082) or by a recombinant adenovirus expressing the nonphosphorylatable form of IkappaB alpha, 804G-ECM-induced cell spreading and actin cytoskeleton organization were reduced. GSIS from cells on 804G-ECM was inhibited 5-fold, whereas cell survival was not affected. In summary, the results indicate that 804G-ECM induces a transient and moderate NF-kappaB activity. This study shows for the first time that ECM-induced NF-kappaB activity is necessary in maintaining GSIS, although it does not affect survival of pancreatic beta cells. The effects of ECM-induced NF-kappaB activity contrast with the deleterious effects of cytokine-induced NF-kappaB activity. It is proposed that transient and moderate NF-kappaB activity is essential for proper function of the pancreatic beta cell.

Keywords
  • Actins/chemistry/metabolism
  • Active Transport, Cell Nucleus
  • Adenoviridae/genetics
  • Animals
  • Antigens, CD29/metabolism
  • Blotting, Western
  • Cell Adhesion Molecules/metabolism
  • Cell Survival
  • Cells, Cultured
  • Cytoskeleton/metabolism
  • DNA/chemistry
  • Enzyme Inhibitors/pharmacology
  • Extracellular Matrix/ metabolism
  • Glucose/ metabolism
  • I-kappa B Proteins/metabolism
  • In Situ Nick-End Labeling
  • Insulin/ metabolism
  • Islets of Langerhans/ metabolism
  • Kinetics
  • Male
  • NF-kappa B/ metabolism
  • Nitriles/pharmacology
  • Phosphorylation
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfones/pharmacology
  • Time Factors
Citation (ISO format)
HAMMAR BOUVERET, Eva et al. Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells. In: The Journal of biological chemistry, 2005, vol. 280, n° 34, p. 30630–30637. doi: 10.1074/jbc.M502493200
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Identifiers
ISSN of the journal0021-9258
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152downloads

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