Extracellular Matrix Protects Pancreatic β-Cells Against Apoptosis

Role of Short- and Long-Term Signaling Pathways

  1. Eva Hammar1,
  2. Géraldine Parnaud1,
  3. Domenico Bosco2,
  4. Nadja Perriraz1,
  5. Kathrin Maedler3,
  6. Marc Donath3,
  7. Dominique G. Rouiller1 and
  8. Philippe A. Halban1
  1. 1Department of Genetic Medicine and Development, University Medical Center, University Hospital, Geneva, Switzerland
  2. 2Cell Isolation and Transplantation Center, University Hospital, Geneva, Switzerland
  3. 3Division of Endocrinology and Diabetes, University Hospital, Zurich, Switzerland
  1. Address correspondence and reprint requests to Eva Hammar, Department of Genetic Medecine and Development, University Medical Center, 9th Floor, Rue Michel Servet 1, 1211 Geneva 4, Switzerland. E-mail: eva.hammar{at}medecine.unige.ch


We have shown previously that culture of β-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 β-cells against apoptosis and to elucidate signaling pathways involved. Matrix protected sorted rat β-cells against apoptosis under standard conditions (11.2 mmol/l glucose, 10% serum), after serum deprivation (1% serum), and in response to interleukin-1β (IL-1β; 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-β1 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-κB (IκBα) 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 β-cell survival.


    • Accepted May 12, 2004.
    • Received January 21, 2004.
| Table of Contents