Teresa Daraio (Author), Lidija Križančić Bombek (Author), Marko Gosak (Author), Ismael Valladolid-Acebes (Author), Maša Skelin (Author), Essam Refai (Author), Per-Olof Berggren (Author), Kerstin Brismar (Author), Marjan Rupnik (Author), Christina Bark (Author)

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 Ca2+ in [beta] cells within pancreatic slices showed no significant differences in Ca2+-sensitivity, amplitude or rate of exocytosis between SNAP-25b-deficient and wild-type littermates. Therefore, we next investigated if Ca2+ handling was affected in glucose-stimulated [beta] cells using intracellular Ca2+-imaging and found premature activation and delayed termination of [Ca2+] i elevations. These findings were accompanied by less synchronized Ca2+-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 Ca2+-dynamics.

Keywords

insulin secretion;pre-diabetes;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UM MF - Faculty of Medicine
UDC: 612.349.7
COBISS: 512737080 Link will open in a new window
ISSN: 2045-2322
Views: 857
Downloads: 129
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Other data

Secondary language: Slovenian
Secondary keywords: Pancreas;physiology;Islets of Langerhans;
URN: URN:SI:UM:
Type (COBISS): Scientific work
Pages: 14 str.
Issue: ǂVol. ǂ7
Chronology: 2017
DOI: 10.1038/s41598-017-08082-y
ID: 10859897