The highly expressed calcium-insensitive synaptotagmin-11 and synaptotagmin-13 modulate insulin secretion

AIM: SYT11 and SYT13, two calcium-insensitive synaptotagmins, are downregulated in islets from type-2 diabetic donors, but their function in insulin secretion is unknown. To address this, we investigated the physiological role of these two synaptotagmins in insulin secreting cells.METHODS: Correlations between gene expression levels were performed using previously described RNA-seq data on islets from 188 human donors. SiRNA knockdown was performed in EndoC-βH1 and INS-1 832/13 cells. Insulin secretion was measured with ELISA. Patch clamp was used for single cell electrophysiology. Confocal microscopy was used to determine intra-cellular localization.RESULTS: Human islet expression of the transcription factor PDX-1 was positively correlated with SYT11 (p = 2.4e -10 ) and SYT13 (p