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Title:SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of $Ca^{2+}$ oscillations in $\beta$ cell networks
Authors:ID Daraio, Teresa (Author)
ID Križančić Bombek, Lidija (Author)
ID Gosak, Marko (Author)
ID Valladolid-Acebes, Ismael (Author)
ID Skelin, Maša (Author)
ID Refai, Essam (Author)
ID Berggren, Per-Olof (Author)
ID Brismar, Kerstin (Author)
ID Rupnik, Marjan (Author)
ID Bark, Christina (Author)
Files:.pdf Scientific_Reports_2017_Daraio_et_al._SNAP-25b-deficiency_increases_insulin_secretion_and_changes_spatiotemporal_profile_of_Ca2oscillati.pdf (3,80 MB)
MD5: B4CD9E1EB06D497213C6589DFAE0217C
PID: 20.500.12556/dkum/52b39900-bc16-4a2c-9076-c00e7f265f1d
 
URL http://www.nature.com/articles/s41598-017-08082-y
 
Language:English
Work type:Scientific work
Typology:1.01 - Original Scientific Article
Organization:MF - Faculty of Medicine
Abstract:SNAP-25 is a protein of the core SNARE complex mediating stimulus-dependent release of insulin from pancreatic $\beta$ cells. The protein exists as two alternatively spliced isoforms, SNAP-25a and SNAP-25b, differing in 9 out of 206 amino acids, yet their specific roles in pancreatic $\beta$ cells remain unclear. We explored the effect of SNAP-25b-deficiency on glucose-stimulated insulin release in islets and found increased secretion both in vivo and in vitro. However, slow photo-release of caged $Ca^{2+}$ in $\beta$ cells within pancreatic slices showed no significant differences in $Ca^{2+}$-sensitivity, amplitude or rate of exocytosis between SNAP-25b-deficient and wild-type littermates. Therefore, we next investigated if $Ca^{2+}$ handling was affected in glucose-stimulated [beta] cells using intracellular $Ca^{2+}$-imaging and found premature activation and delayed termination of [$Ca^{2+}$] i elevations. These findings were accompanied by less synchronized $Ca^{2+}$-oscillations and hence more segregated functional $\beta$ cell networks in SNAP-25b-deficient mice. Islet gross morphology and architecture were maintained in mutant mice, although sex specific compensatory changes were observed. Thus, our study proposes that SNAP-25b in pancreatic [beta] cells, except for participating in the core SNARE complex, is necessary for accurate regulation of $Ca^{2+}$-dynamics.
Keywords:insulin secretion, pre-diabetes
Publication status:Published
Publication version:Version of Record
Year of publishing:2017
Number of pages:str. 1-14
Numbering:Letn. 7
PID:20.500.12556/DKUM-67558 New window
ISSN:2045-2322
UDC:612.349.7
ISSN on article:2045-2322
COBISS.SI-ID:512737080 New window
DOI:10.1038/s41598-017-08082-y New window
NUK URN:URN:SI:UM:DK:JCTVXOKB
Publication date in DKUM:23.08.2017
Views:1454
Downloads:203
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Categories:Misc.
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Record is a part of a journal

Title:Scientific reports
Shortened title:Sci. rep.
Publisher:Nature Publishing Group
ISSN:2045-2322
COBISS.SI-ID:18727432 New window

Document is financed by a project

Funder:ARRS - Slovenian Research Agency
Project number:P3-0396
Name:Celične in tkivne mreže

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:23.08.2017

Secondary language

Language:Slovenian
Keywords:izločanje inzulina, prediabetes


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