Syntaxin 4 facilitates biphasic glucose-stimulated insulin secretion from pancreatic β-cells

Beth A. Spurlin, Debbie C. Thurmond

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Numerous overexpression studies have recently implicated Syntaxin 4 as an effector of insulin secretion, although its requirement in insulin granule exocytosis is unknown. To address this, islets from Syntaxin 4 heterozygous (-/+) knockout mice were isolated and compared with islets from wildtype mice. Under static incubation conditions, Syntaxin 4 (-/+) islets showed a 60% reduction in glucose-stimulated insulin secretion compared with wild-type islets. Perifusion analyses revealed that Syntaxin 4 (-/+) islets secreted 50% less insulin during the first phase of glucose-stimulated insulin secretion and that this defect could be fully restored by the specific replenishment of recombinant Syntaxin 4. This essential role for Syntaxin 4 in secretion from the islet was localized to the β-cells because small interfering RNA-mediated depletion of Syntaxin 4 in MIN6 β-cells abolished glucose-stimulated insulin secretion. Moreover, immunofluorescent confocal microscopy revealed that Syntaxin 4 was principally localized to the β-cells and not the α-cells of the mouse islet. Remarkably, islets isolated from transgenic mice that express 2.4-fold higher levels of Syntaxin 4 relative to wild-type mice secreted approximately 35% more insulin during both phases of insulin secretion, suggesting that increased Syntaxin 4 may be beneficial for enhancing biphasic insulin secretion in a regulated manner. Taken together, these data support the notion that Syntaxin 4-based SNARE complexes are essential for biphasic insulin granule fusion in pancreatic β-cells.

Original languageEnglish
Pages (from-to)183-193
Number of pages11
JournalMolecular Endocrinology
Volume20
Issue number1
DOIs
StatePublished - Jan 2006

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Qa-SNARE Proteins
Insulin
Glucose
Biphasic Insulins
SNARE Proteins
Exocytosis
Islets of Langerhans
Knockout Mice
Confocal Microscopy
Small Interfering RNA
Transgenic Mice

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Syntaxin 4 facilitates biphasic glucose-stimulated insulin secretion from pancreatic β-cells. / Spurlin, Beth A.; Thurmond, Debbie C.

In: Molecular Endocrinology, Vol. 20, No. 1, 01.2006, p. 183-193.

Research output: Contribution to journalArticle

Spurlin, Beth A. ; Thurmond, Debbie C. / Syntaxin 4 facilitates biphasic glucose-stimulated insulin secretion from pancreatic β-cells. In: Molecular Endocrinology. 2006 ; Vol. 20, No. 1. pp. 183-193.
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