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

Mol Endocrinol. 2006 Jan;20(1):183-93. doi: 10.1210/me.2005-0157. Epub 2005 Aug 11.


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 wild-type 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 beta-cells because small interfering RNA-mediated depletion of Syntaxin 4 in MIN6 beta-cells abolished glucose-stimulated insulin secretion. Moreover, immunofluorescent confocal microscopy revealed that Syntaxin 4 was principally localized to the beta-cells and not the alpha-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 beta-cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cricetinae
  • Glucose / pharmacology
  • Glucose / physiology*
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans / metabolism*
  • Male
  • Mice
  • Mice, Transgenic
  • Qa-SNARE Proteins / genetics
  • Qa-SNARE Proteins / metabolism*
  • RNA, Small Interfering / genetics


  • Insulin
  • Qa-SNARE Proteins
  • RNA, Small Interfering
  • Glucose