| Title: | SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of $Ca^{2+}$ oscillations in $\beta$ cell networks |
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| 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) |
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| Files: |  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
 http://www.nature.com/articles/s41598-017-08082-y
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| Language: | English |
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| Work type: | Scientific work |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | MF - Faculty of Medicine
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| 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. |
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| Keywords: | insulin secretion, pre-diabetes |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2017 |
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| Number of pages: | str. 1-14 |
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| Numbering: | Letn. 7 |
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| PID: | 20.500.12556/DKUM-67558  |
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| ISSN: | 2045-2322 |
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| UDC: | 612.349.7 |
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| ISSN on article: | 2045-2322 |
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| COBISS.SI-ID: | 512737080 |
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| DOI: | 10.1038/s41598-017-08082-y |
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| NUK URN: | URN:SI:UM:DK:JCTVXOKB |
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| Publication date in DKUM: | 23.08.2017 |
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| Views: | 1663 |
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| Downloads: | 255 |
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| Metadata: |    |
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| Categories: | Misc.
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