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Scientific article
English

Glucose-stimulated insulin secretion is coupled to the interaction of actin with the t-SNARE (target membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein) complex

Published inMolecular endocrinology, vol. 17, no. 4, p. 732-742
Publication date2003
Abstract

The actin monomer sequestering agent latrunculin B depolymerized beta-cell cortical actin, which resulted in increased glucose-stimulated insulin secretion in both cultured MIN6 beta-cells and isolated rat islet cells. In perifused islets, latrunculin B treatment increased both first- and second-phase glucose-stimulated insulin secretion without any significant effect on total insulin content. This increase in secretion was independent of calcium regulation because latrunculin B also potentiated calcium-stimulated insulin secretion in permeabilized MIN6 cells. Confocal immunofluorescent microscopy revealed a redistribution of insulin granules to the cell periphery in response to glucose or latrunculin B, which correlated with a reduction in phalloidin staining of cortical actin. Moreover, the t-SNARE [target membrane soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor] proteins Syntaxin 1 and SNAP-25 coimmunoprecipitated polymerized actin from unstimulated MIN6 cells. Glucose stimulation transiently decreased the amount of actin coimmunoprecipitated with Syntaxin 1 and SNAP-25, and latrunculin B treatment fully ablated the coimmunoprecipitation. In contrast, the actin stabilizing agent jasplakinolide increased the amount of actin coimmunoprecipitated with the t-SNARE complex and prevented its dissociation upon glucose stimulation. These data suggest a mechanism whereby glucose modulates beta-cell cortical actin organization and disrupts the interaction of polymerized actin with the plasma membrane t-SNARE complex at a distal regulatory step in the exocytosis of insulin granules.

Keywords
  • Actins/drug effects/ metabolism
  • Animals
  • Antigens, Surface/metabolism
  • Bicyclo Compounds, Heterocyclic/pharmacology
  • Calcium/metabolism
  • Calcium Channels/metabolism
  • Cells, Cultured
  • Cytoplasmic Granules/metabolism
  • Glucose/ metabolism/pharmacology
  • Insulin/ secretion
  • Islets of Langerhans/drug effects/metabolism/secretion
  • Membrane Proteins/ metabolism
  • Nerve Tissue Proteins/metabolism
  • Perfusion
  • Precipitin Tests
  • R-SNARE Proteins
  • Rats
  • SNARE Proteins
  • Synaptosomal-Associated Protein 25
  • Syntaxin 1
  • Thiazoles/pharmacology
  • Thiazolidines
  • Vesicular Transport Proteins
Citation (ISO format)
THURMOND, D. C. et al. Glucose-stimulated insulin secretion is coupled to the interaction of actin with the t-SNARE (target membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein) complex. In: Molecular endocrinology, 2003, vol. 17, n° 4, p. 732–742. doi: 10.1210/me.2002-0333
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ISSN of the journal0888-8809
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