Affordable Access

Publisher Website

Focal adhesion remodeling is crucial for glucose-stimulated insulin secretion and involves activation of focal adhesion kinase and paxillin.

Authors
  • Rondas, D
  • Tomas, A
  • Halban, PA
Publication Date
Apr 01, 2011
Identifiers
DOI: 10.2337/db10-0946
OAI: oai:spiral.imperial.ac.uk:10044/1/42214
Source
UPCommons. Portal del coneixement obert de la UPC
Keywords
Language
English
License
Unknown

Abstract

OBJECTIVE: Actin cytoskeleton remodeling is known to be involved in glucose-stimulated insulin secretion (GSIS). We have observed glucose-stimulated changes at the β-cell basal membrane similar to focal adhesion remodeling in cell migration. This led us to study the role of two key focal adhesion proteins, focal adhesion kinase (FAK) and paxillin, in GSIS. RESEARCH DESIGN AND METHODS: All studies were performed using rat primary β-cells or isolated islets. Protein phosphorylation and subcellular localization were determined by Western blotting and confocal immunofluorescence, respectively. Insulin was measured by radioimmunoassay. Both siRNA and pharmacological approaches were used to assess the role of FAK and paxillin in glucose-stimulated focal adhesion remodeling and insulin secretion. RESULTS: Glucose stimulation of β-cells in monolayer significantly increased phosphorylation of FAK and paxillin as well as cell surface area. This coincided with the appearance at the basal membrane of numerous shorter actin filopodial extensions, containing not only phosphorylated paxillin, FAK, and extracellular signal-related kinase 1/2 but also two SNARE proteins, synaptosomal-associated protein 25 and syntaxin 1, indicating involvement in exocytosis. SR7037 completely inhibited this sequence of events, indicating the requirement of increased cytosolic Ca²(+). Furthermore, knockdown of paxillin significantly decreased GSIS, as did inhibition of glucose-induced FAK phosphorylation by compound Y15. Key findings were confirmed in β-cells within the natural setting of islets. CONCLUSIONS: Glucose-stimulated remodeling of focal adhesions and phosphorylation of FAK and paxillin are involved in full development of GSIS, indicating a previously unknown role for focal adhesion remodeling in pancreatic β-cell function.

Report this publication

Statistics

Seen <100 times