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 β‐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 β‐cell secretion.