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


ABSTRACT: Actin cytoskeleton remodeling is well known to be positively involved in glucose-stimulated pancreatic ? cell insulin secretion. We have observed glucose-stimulated focal adhesion remodeling at the ? 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 ? 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 ?1 at the basal cell surface after short term stimulation. In addition, blockade of the interaction between ?1 integrins and the extracellular matrix with an anti-?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 ?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.

SUBMITTER: Rondas D 

PROVIDER: S-EPMC3268403 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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

Rondas Dieter D   Tomas Alejandra A   Soto-Ribeiro Martinho M   Wehrle-Haller Bernhard B   Halban Philippe A PA  

The Journal of biological chemistry 20111202 4


Actin cytoskeleton remodeling is well known to be positively involved in glucose-stimulated pancreatic β cell insulin secretion. We have observed glucose-stimulated focal adhesion remodeling at the β 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 β cell functi  ...[more]

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