title: Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1), a hormone with potent antihyperglycaemic effects, is produced and secreted from highly specialised gut endocrine L-cells. It regulates glucose homeostasis by promoting glucose-dependent insulin secretion, suppressing glucagon secretion and enhancing insulin sensitivity. Similar to islet alpha and beta cells, L-cells are electrically excitable, and express calcium channels and ATP-sensitive potassium channels. GLP-1 is also stored in secretory granules, the exocytosis of which is triggered by increased intracellular calcium levels. Although the calcium dependence of GLP-1 granule exocytosis is well established, the identities of calcium-sensing proteins in GLP-1 secretion remain elusive. Here we tested whether synaptotagmin-7, a calcium sensor in pancreatic alpha and beta cells, regulates GLP-1 secretion.
  
  
  METHODS
  We studied GLP-1 secretion using synaptotagmin-7 knockout (KO) mice and GLUTag cells with lentiviral-mediated synaptotagmin-7 silencing.
  
  
  RESULTS
  We found that synaptotagmin-7 was co-localised with GLP-1 in intestinal L-cells. GLP-1 secretion was impaired in synaptotagmin-7 KO mice when they were challenged by glucose ingestion. Lentiviral knockdown (KD) of synaptotagmin-7 in GLUTag cells led to similar reductions in GLP-1 secretion, as determined by biochemical assays and by membrane capacitance measurements. Calcium response was not altered in synaptotagmin-7 KD cells.
  
  
  CONCLUSIONS
  These results demonstrate that synaptotagmin-7 functions as a positive regulator of GLP-1 secretion in intestinal L-cells and GLUTag cells, consistent with its proposed role as a calcium sensor in GLP-1 secretion.
authors.affiliation: Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A STAR), 02-02 Helios, 11 Biopolis Way, Singapore, 138667, Republic of Singapore.
authors.forename: N
authors.initials: N
authors.lastname: Gustavsson
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Kang
authors.forename: T
authors.initials: T
authors.lastname: Seah
authors.forename: S
authors.initials: S
authors.lastname: Chua
authors.forename: G K
authors.initials: GK
authors.lastname: Radda
authors.forename: W
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004594:Electrophysiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D007150:Immunohistochemistry; D007422:Intestines / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000235:genetics; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D050857:Synaptotagmins; D052216:Glucagon-Like Peptide 1