Role of synaptotagmin-7 in glucagon-like peptide (GLP-1) secretion.

Abstract

Glucagon-like peptide-1 (GLP-1), produced by intestinal L cells, is an important incretin with insulinotropic properties. Recent studies have highlighted the possibilities of GLP-1 based treatment for Type 2 Diabetes Mellitus. However, molecular mechanism of GLP-1 secretion regulation remains to be elucidated. Synaptotagmins is a family of membrane trafficking proteins consisting of 15 different isoforms. Among the different synaptotagmin isoforms, the function of synaptotagmin-1, -2 and -9 as calcium sensor in regulating exocytosis of neurotransmitter and Synaptotagmin-7 as calcium sensor in neuropeptide and hormone secretion have been well characterized. The calcium sensor role of other synaptotagmin isoforms remains to be explored. Considering Synaptotagmin-7’s function role as a calcium sensor in regulating the exocytosis of large dense core vesicles, we investigated whether synaptotagmin-7 has a function as a calcium sensor in regulating calcium-triggered GLP-1 secretion. Here, we examined the effect of synaptotagmin-7 knockdown on GLP-1 secretion using a L-cell model, GLUTag. In addition, we analysed analysis on GLP-1 secretion in synaptotagmin-7 mutant mice. Results from these studies revealed a possible role of synaptotagmin-7 as a calcium sensor in regulating GLP-1 exocytosis.