SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of Ca2+oscillations in β cell networks
Abstract SNAP-25 is a protein of the core SNARE complex mediating stimulus-dependent release of insulin from pancreatic β 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 β cells rema...
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2017
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oai:doaj.org-article:7e4eb908326647c698fc9da6dd4b90752021-12-02T12:31:50ZSNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of Ca2+oscillations in β cell networks10.1038/s41598-017-08082-y2045-2322https://doaj.org/article/7e4eb908326647c698fc9da6dd4b90752017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08082-yhttps://doaj.org/toc/2045-2322Abstract SNAP-25 is a protein of the core SNARE complex mediating stimulus-dependent release of insulin from pancreatic β 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 β 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 β 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 β 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 β 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 β cells, except for participating in the core SNARE complex, is necessary for accurate regulation of Ca2+-dynamics.Teresa DaraioLidija Križančić BombekMarko GosakIsmael Valladolid-AcebesMaša Skelin KlemenEssam RefaiPer-Olof BerggrenKerstin BrismarMarjan Slak RupnikChristina BarkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Teresa Daraio Lidija Križančić Bombek Marko Gosak Ismael Valladolid-Acebes Maša Skelin Klemen Essam Refai Per-Olof Berggren Kerstin Brismar Marjan Slak Rupnik Christina Bark SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of Ca2+oscillations in β cell networks |
| description |
Abstract SNAP-25 is a protein of the core SNARE complex mediating stimulus-dependent release of insulin from pancreatic β 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 β 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 β 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 β 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 β 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 β cells, except for participating in the core SNARE complex, is necessary for accurate regulation of Ca2+-dynamics. |
| format |
article |
| author |
Teresa Daraio Lidija Križančić Bombek Marko Gosak Ismael Valladolid-Acebes Maša Skelin Klemen Essam Refai Per-Olof Berggren Kerstin Brismar Marjan Slak Rupnik Christina Bark |
| author_facet |
Teresa Daraio Lidija Križančić Bombek Marko Gosak Ismael Valladolid-Acebes Maša Skelin Klemen Essam Refai Per-Olof Berggren Kerstin Brismar Marjan Slak Rupnik Christina Bark |
| author_sort |
Teresa Daraio |
| title |
SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of Ca2+oscillations in β cell networks |
| title_short |
SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of Ca2+oscillations in β cell networks |
| title_full |
SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of Ca2+oscillations in β cell networks |
| title_fullStr |
SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of Ca2+oscillations in β cell networks |
| title_full_unstemmed |
SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of Ca2+oscillations in β cell networks |
| title_sort |
snap-25b-deficiency increases insulin secretion and changes spatiotemporal profile of ca2+oscillations in β cell networks |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/7e4eb908326647c698fc9da6dd4b9075 |
| work_keys_str_mv |
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