20.500.12556/DKUM-67558 SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of $Ca^{2+}$ oscillations in $\beta$ cell networks 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. insulin secretion pre-diabetes izločanje inzulina prediabetes true false true Angleški jezik Slovenski jezik Znanstveno delo 2017-08-23 09:32:32 2017-08-23 09:38:05 2022-08-01 14:08:04 2019-07-11 16:24:29 2017 0 0 str. 1-14 Letn. 7 2017 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 2045-2322 612.349.7 18727432 512737080 10.1038/s41598-017-08082-y 2045-2322 URN:SI:UM:DK:JCTVXOKB Scientific_Reports_2017_Daraio_et_al._SNAP-25b-deficiency_increases_insulin_secretion_and_changes_spatiotemporal_profile_of_Ca2oscillati.pdf Scientific_Reports_2017_Daraio_et_al._SNAP-25b-deficiency_increases_insulin_secretion_and_changes_spatiotemporal_profile_of_Ca2oscillati.pdf 1 B4CD9E1EB06D497213C6589DFAE0217C 85482f24310b91f82c61d643db44a6e25e93843deab14a095d72c9314fd9e9bb 8b184f7a-7c0e-11eb-bb7a-00155d0001ca 20.500.12556/dkum/52b39900-bc16-4a2c-9076-c00e7f265f1d https://dk.um.si/Dokument.php?lang=slv&id=115758 http://www.nature.com/articles/s41598-017-08082-y 1 https://dk.um.si/Dokument.php?lang=slv&id=115757 Medicinska fakulteta 0 0 0