Scientific Reports (Aug 2017)

SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of Ca2+oscillations in β cell networks

  • 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

DOI
https://doi.org/10.1038/s41598-017-08082-y
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 14

Abstract

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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.