| First Author | Daraio T | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 7744 |
| PubMed ID | 28798351 | Mgi Jnum | J:275260 |
| Mgi Id | MGI:6296321 | Doi | 10.1038/s41598-017-08082-y |
| Citation | Daraio T, et al. (2017) SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of Ca(2+)oscillations in beta cell networks. Sci Rep 7(1):7744 |
| abstractText | 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. |
