en
Scientific article
English

Blockade of beta1 integrin-laminin-5 interaction affects spreading and insulin secretion of rat beta-cells attached on extracellular matrix

Published inDiabetes, vol. 55, no. 5, p. 1413-1420
Publication date2006
Abstract

When attached on a matrix produced by a rat bladder carcinoma cell line (804G matrix), rat pancreatic beta-cells spread in response to glucose and secrete more insulin compared with cells attached on poly-l-lysine. The aim of this study was to determine whether laminin-5 and its corresponding cell receptor beta1 integrin are implicated in these phenomena. By using specific blocking antibodies, we demonstrated that laminin-5 is the component present in 804G matrix responsible for the effect of 804G matrix on beta-cell function and spreading. When expression of two well-known laminin-5 ligands, beta1 and beta4 integrin, was assessed by Western blot and RT-PCR, only the beta1 integrin was detected in beta-cells. Anti-beta1 integrin antibody reduced the spreading of beta-cells on 804G matrix. Blockade of the interaction between beta1 integrins and laminin-5 resulted in a reduction in glucose-stimulated insulin secretion. Blocking anti-beta1 integrin antibody also inhibited focal adhesion kinase phosphorylation induced by 804G matrix. In conclusion, anti-beta1 integrin and -laminin-5 antibodies interfere with spreading of beta-cells, resulting in decreased insulin secretion in response to glucose. Our findings indicate that outside-in signaling via engagement of beta1 integrins by laminin-5 is an important component of normal beta-cell function.

Keywords
  • Animals
  • Antibodies/pharmacology
  • Antigens, CD29/drug effects/genetics/ physiology
  • Base Sequence
  • Cell Adhesion/drug effects/ physiology
  • Cell Line
  • Cell Movement/physiology
  • Cells, Cultured
  • DNA Primers
  • Extracellular Matrix/drug effects/ physiology
  • Hemolytic Plaque Technique
  • Insulin/ secretion
  • Integrin beta4/genetics
  • Islets of Langerhans/drug effects/ physiology/secretion
  • Laminin/ antagonists & inhibitors/genetics
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
Citation (ISO format)
PARNAUD, Géraldine et al. Blockade of beta1 integrin-laminin-5 interaction affects spreading and insulin secretion of rat beta-cells attached on extracellular matrix. In: Diabetes, 2006, vol. 55, n° 5, p. 1413–1420. doi: 10.2337/db05-1388
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ISSN of the journal0012-1797
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