Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice

Abstract

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.