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English

Extracellular matrix protects pancreatic beta-cells against apoptosis: role of short- and long-term signaling pathways

Contributors

Hammar Bouveret, Eva; Parnaud, Géraldine; Bosco, Domenico; Perriraz-Mayer, Nadja; Maedler, Kathrin; Donath, Marc; Rouiller, Dominique; Halban, Philippe A.

Published in

Diabetes, vol. 53, no. 8, p. 2034-2041

Publication date

2004

Abstract

We have shown previously that culture of beta-cells on matrix derived from 804G cells and rich in laminin-5 improves their function. The purpose of this study was to investigate whether this matrix protects beta-cells against apoptosis and to elucidate signaling pathways involved. Matrix protected sorted rat beta-cells against apoptosis under standard conditions (11.2 mmol/l glucose, 10% serum), after serum deprivation (1% serum), and in response to interleukin-1beta (IL-1beta; 2 ng/ml), compared with control (poly-L-lysine [pLL]). Caspase-8 activity was reduced in cells cultured on matrix, whereas focal adhesion kinase (FAK), protein kinase B (PKB, or Akt), and extracellular signal-regulated kinase (ERK) phosphorylation was augmented. Treatment (4 h) with an anti-beta1 integrin antibody, with the ERK pathway inhibitor PD98059, and/or with the phosphatidylinositol 3-kinase inhibitor LY294002 augmented cell death on 804G matrix but not on pLL. In long-term assays (48 h), PD98059 but not LY294002 drastically augmented cell death on 804G matrix but did so to a lesser extent on pLL. The protein inhibitor of nuclear factor-kappaB (IkappaBalpha) was overexpressed in cells cultured 18 h on matrix with partial blockade by PD98059. In summary, this study provides evidence for activation of signaling pathways and gene expression by extracellular matrix leading to improved beta-cell survival.

Keywords

  • Animals
  • Apoptosis/drug effects/ physiology
  • Caspase 8
  • Caspases/metabolism
  • Culture Media
  • Culture Media, Serum-Free
  • Extracellular Matrix/ physiology
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Interleukin-1/pharmacology
  • Islets of Langerhans/ cytology/drug effects
  • Mitogen-Activated Protein Kinases/metabolism
  • Polylysine/pharmacology
  • Protein-Serine-Threonine Kinases/metabolism
  • Protein-Tyrosine Kinases/metabolism
  • Proto-Oncogene Proteins/metabolism
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Signal Transduction

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

HAMMAR BOUVERET, Eva et al. Extracellular matrix protects pancreatic beta-cells against apoptosis: role of short- and long-term signaling pathways. In: Diabetes, 2004, vol. 53, n° 8, p. 2034–2041. doi: 10.2337/diabetes.53.8.2034

Main files (1)

Article (Published version)

Identifiers

Additional URL for this publication

http://diabetes.diabetesjournals.org/content/53/8/2034.full.pdf

Journal ISSN

0012-1797
656views
792downloads

Technical informations

Creation

12/07/2010 11:58:11

First validation

12/07/2010 11:58:11

Update

14/08/2024 08:18:20

Status update

14/08/2024 08:18:20

Last indexation

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