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Diabetologia. 2013 Feb;56(2):359-69. doi: 10.1007/s00125-012-2757-0. Epub 2012 Nov 7.

Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in pancreatic beta cells.

Author information

1
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Abstract

AIMS/HYPOTHESIS:

The molecular basis of the exocytosis of secretory insulin-containing granules (SGs) during biphasic glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells remains unclear. Syntaxin (SYN)-1A and SYN-4 have been shown to mediate insulin exocytosis. The insulin-secretory function of SYN-3, which is particularly abundant in SGs, is unclear.

METHODS:

Mouse pancreatic islets and INS-1 cells were treated with adenovirus carrying Syn-3 (also known as Stx3) or small interfering RNA targeting Syn-3 in order to examine insulin secretion by radioimmunoassay. The localisation and distribution of insulin granules were examined by confocal and electron microscopy. Dynamic single-granule fusion events were assessed using total internal reflection fluorescence microscopy (TIRFM).

RESULTS:

Depletion of endogenous SYN-3 inhibited insulin release. TIRFM showed no change in the number or fusion competence of previously docked SGs but, instead, a marked reduction in the recruitment of newcomer SGs and their subsequent exocytotic fusion during biphasic GSIS. Conversely, overexpression of Syn-3 enhanced both phases of GSIS, owing to the increase in newcomer SGs and, remarkably, to increased SG-SG fusion, which was confirmed by electron microscopy.

CONCLUSIONS/INTERPRETATION:

In insulin secretion, SYN-3 plays a role in the mediation of newcomer SG exocytosis and SG-SG fusion that contributes to biphasic GSIS.

PMID:
23132338
DOI:
10.1007/s00125-012-2757-0
[Indexed for MEDLINE]

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