GLP1receptor

GLP-1 receptor, abbreviated GLP1R, is a class B G protein-coupled receptor that binds glucagon-like peptide-1 (GLP-1). It is encoded by the GLP1R gene in humans and is expressed in multiple tissues, with high levels in pancreatic beta cells as well as in the brain, gastrointestinal tract, and heart. The receptor mediates many of the physiological effects attributed to GLP-1.

Upon activation by GLP-1 or GLP-1 receptor agonists, GLP1R primarily couples to Gs proteins, stimulating adenylyl cyclase and increasing intracellular cyclic AMP. This triggers signaling pathways involving protein kinase A (PKA) and Epac, leading to glucose-dependent enhancement of insulin secretion from pancreatic beta cells, suppression of glucagon release, slowing of gastric emptying, and reduced appetite. In the central nervous system, GLP1R signaling influences energy balance and could contribute to anorectic effects observed with GLP-1-based therapies. The receptor is also involved in other physiological processes, including cardiovascular regulation and possibly neuroprotection.

Endogenous GLP-1 is secreted by intestinal L cells in response to meals but is rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Clinically, GLP-1 receptor agonists (e.g., exenatide, liraglutide, dulaglutide, lixisenatide, albiglutide, semaglutide) provide longer-lasting activation and are used to treat type 2 diabetes and, in some cases, obesity. The pharmacokinetic profiles vary among agents, with some available as injections and, for semaglutide, a recent oral formulation is also approved.

Therapeutically, GLP1R agonists improve glycemic control and often promote weight loss, with common adverse effects including nausea and gastrointestinal symptoms. Safety monitoring continues for rare risks such as pancreatitis. Research on GLP1R spans metabolic, cardiovascular, and potential neurodegenerative applications.