Adenovirus-mediated silencing of Synaptotagmin 9 inhibits Ca2+-dependent insulin secretion in islets

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Abstract

Synaptotagmins (Syts) are involved in Ca2+-dependent insulin release. However, which Syt isoform is functional in primary beta-cells remains unknown. We demonstrate by electron microscopy of pancreatic islets, the association of Syt 9 with insulin granules. Silencing of Syt 9 by RNA interference adenovirus in islet cells had no effect on the expression of Syt 5, Syt 7 and Syt 3 isoforms. The latter was localized at the plasma membrane of pancreatic polypeptide cells. Insulin release in response to glucose or tolbutamide was strongly inhibited in Syt 9 deficient islets, whereas exocytosis potentiated by raising cAMP levels, was unaltered. Thus, Syt 9 may act as Ca2+ sensor for beta-cell secretion.

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Subject classification (UKÄ) – MANDATORY

  • Biological Sciences

Keywords

  • insulin exocytosis, pancreatic islets, electron, RNA, microscopy, interference, beta-cell
Original languageEnglish
Pages (from-to)5241-5246
JournalFEBS Letters
Volume579
Issue number23
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes