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

Debbie C. Thurmond, Carmen Gonelle-Gispert, Megumi Furukawa, Philippe A. Halban, Jeffrey E. Pessin

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

The actin monomer sequestering agent latrunculin B depolymerized β-cell cortical actin, which resulted in increased glucose-stimulated insulin secretion in both cultured MIN6 β-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 β-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.

Original languageEnglish (US)
Pages (from-to)732-742
Number of pages11
JournalMolecular Endocrinology
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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