

Other version: http://mend.endojournals.org/cgi/reprint/17/4/732.pdf
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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 |
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Published in | Molecular endocrinology. 2003, vol. 17, no. 4, p. 732-742 | |
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 | |
Identifiers | DOI: 10.1210/me.2002-0333 PMID: 12554769 | |
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![]() ![]() Other version: http://mend.endojournals.org/cgi/reprint/17/4/732.pdf |
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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 https://archive-ouverte.unige.ch/unige:9055 |