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

Povzetek

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.

Ključne besede

insulin secretion;pre-diabetes;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UM MF - Medicinska fakulteta
UDK: 612.349.7
COBISS: 512737080 Povezava se bo odprla v novem oknu
ISSN: 2045-2322
Št. ogledov: 857
Št. prenosov: 129
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: Pancreas;physiology;Islets of Langerhans;
URN: URN:SI:UM:
Vrsta dela (COBISS): Znanstveno delo
Strani: 14 str.
Zvezek: ǂVol. ǂ7
Čas izdaje: 2017
DOI: 10.1038/s41598-017-08082-y
ID: 10859897