Glucagon-like peptide 2 (GLP2) acts through G protein-coupled receptor GLP2R and plays a physiological role in the control of food intake and glucose homeostasis. It promotes intestinal epithelial homeostasis and function, enhances intestinal nutrient absorption and blood flow and assists gut immune defense []. GLP2R is not only expressed in nutrient-sensing endocrine cells (such as enteroendocrine cells and pancreatic alpha-cells), but also in neurons [, , ]. GLP2R in hypothalamic POMC neurons is required for promoting hepatic insulin sensitivity and glycemic control. Through GLP2R-p85alpha interaction, GLP2 activates PI3K-Akt-FoxO1 signaling in POMC neurons [].
