Novel mechanistic link between focal adhesion remodeling and glucose-stimulated insulin secretion

Autor: Philippe A. Halban, Dieter Rondas, Martinho Soto-Ribeiro, Bernhard Wehrle-Haller, Alejandra Tomas
Rok vydání: 2012
Předmět:
Focal Adhesions/genetics/metabolism
medicine.medical_treatment
Biochemistry
Antigens
CD29/genetics/metabolism
chemistry.chemical_compound
0302 clinical medicine
Insulin-Secreting Cells
Insulin Secretion
Insulin
ddc:576.5
Signal Transduction/drug effects/genetics
Cytoskeleton
0303 health sciences
Mitogen-Activated Protein Kinase 3
biology
Integrin beta1
GTPase-Activating Proteins
pancreatic beta-cells
11 Medical And Health Sciences
Insulin/genetics/secretion
evanescent-wave microscopy
Glucose/pharmacology
Cell biology
Actins/genetics/metabolism
Focal Adhesion Kinase 1/genetics/metabolism
GTPase-Activating Proteins/genetics/metabolism
Insulin-Secreting Cells/cytology/metabolism
Signal transduction
binding proteins
03 Chemical Sciences
Proto-Oncogene Proteins c-akt/genetics/metabolism
small-molecule inhibitor
Signal Transduction
signal-transduction
Biochemistry & Molecular Biology
Synaptosomal-Associated Protein 25
Integrin
030209 endocrinology & metabolism
rho-subfamily
Focal adhesion
03 medical and health sciences
Cell Line
Tumor
medicine
Animals
Sweetening Agents/pharmacology
extracellular-matrix
ddc:612
Molecular Biology
Protein kinase B
Paxillin
030304 developmental biology
Focal Adhesions
Synaptosomal-Associated Protein 25/genetics/metabolism
skeletal-muscle cells
tyrosine phosphorylation
Antigens
CD29
Paxillin/genetics/metabolism
Tyrosine phosphorylation
Cell Biology
06 Biological Sciences
Actins
Rats
Glucose
gtpase-activating protein
chemistry
Focal Adhesion Kinase 1
Sweetening Agents
Cytoskeleton/genetics/metabolism
biology.protein
Proto-Oncogene Proteins c-akt
Mitogen-Activated Protein Kinase 3/genetics/metabolism
Zdroj: The Journal of biological chemistry
Journal of Biological Chemistry, Vol. 287, No 4 (2012) pp. 2423-36
ISSN: 0021-9258
DOI: 10.1074/jbc.M111.279885
Popis: Actin cytoskeleton remodeling is well known to be positively involved in glucose-stimulated pancreatic beta cell insulin secretion. We have observed glucose-stimulated focal adhesion remodeling at the beta cell surface and have shown this to be crucial for glucose-stimulated insulin secretion. However, the mechanistic link between such remodeling and the insulin secretory machinery remained unknown and was the major aim of this study. MIN6B1 cells, a previously validated model of primary beta cell function, were used for all experiments. Total internal reflection fluorescence microscopy revealed the glucose-responsive co-localization of focal adhesion kinase (FAK) and paxillin with integrin beta 1 at the basal cell surface after short term stimulation. In addition, blockade of the interaction between beta 1 integrins and the extracellular matrix with an anti-beta 1 integrin antibody (Ha2/5) inhibited short term glucose-induced phosphorylation of FAK (Tyr-397), paxillin (Tyr-118), and ERK1/2 (Thr-202/Tyr-204). Pharmacological inhibition of FAK activity blocked glucose-induced actin cytoskeleton remodeling and glucose-induced disruption of the F-actin/SNAP-25 association at the plasma membrane as well as the distribution of insulin granules to regions in close proximity to the plasma membrane. Furthermore, FAK inhibition also completely blocked short term glucose-induced activation of the Akt/AS160 signaling pathway. In conclusion, these results indicate 1) that glucose-induced activation of FAK, paxillin, and ERK1/2 is mediated by beta 1 integrin intracellular signaling, 2) a mechanism whereby FAK mediates glucose-induced actin cytoskeleton remodeling, hence allowing docking and fusion of insulin granules to the plasma membrane, and 3) a possible functional role for the Akt/AS160 signaling pathway in the FAK-mediated regulation of glucose-stimulated insulin secretion. ispartof: Journal of Biological Chemistry vol:287 issue:4 pages:2423-2436 ispartof: location:United States status: published
Databáze: OpenAIRE
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