Synaptotagmin-7 in the regulation of hormone secretion.

Abstract

Blood glucose control is important to maintain energy supply and utilization in the body and relies on highly regulated hormone secretion. Hormones involved include insulin, glucagon and glucagon-like peptide-1 (GLP-1), in which the dysregulation of insulin and glucagon results in diabetes mellitus while GLP-1 is a potential therapy against diabetes mellitus. The molecular mechanisms of these hormone secretion regulations have been gradually elucidated over the years. Synaptotagmin-7 (Syt-7) of the synaptotagmin family consisting of at least 15 members has been identified as the principal calcium sensor in regulating exocytosis of these hormones. Previous studies showed that the knocked down of Syt-7 in mice resulted in decreased insulin and glucagon secretions and the deletion of Syt-7 in GLUTag cells reduced GLP-1 secretion. Therefore, we employed lentiviral-mediated delivery of Syt-7 into Syt-7 knock-out (KO) mouse pancreatic islets to restore Syt-7 expression as well as to overexpress Syt-7 in GLUTag cells, and observing the effects on glucagon, insulin and GLP-1 secretions. We observed the restoration of glucagon secretion in Syt-7 KO islets after Syt-7 expression and the possible amplification of GLP-1 secretion in GLUTag cells after Syt-7 overexpression. Hence, this further supports the importance of Syt-7 in the exocytosis of glucagon and GLP-1.