Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice
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AIMS/HYPOTHESIS: 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/INTERPRETATION: 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.
Original language | English |
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Journal | Diabetologia |
Volume | 54 |
Issue number | 7 |
Pages (from-to) | 1824-30 |
Number of pages | 7 |
ISSN | 0012-186X |
DOIs | |
Publication status | Published - Jul 2011 |
- Animals, Blotting, Western, Cells, Cultured, Electrophysiology, Glucagon-Like Peptide 1, Immunohistochemistry, Intestines, Mice, Mice, Knockout, Polymerase Chain Reaction, RNA, Small Interfering, Synaptotagmins, Journal Article, Research Support, Non-U.S. Gov't
Research areas
ID: 172513150