Glucagon-like peptide-1 (GLP-1)

Glucagon-like peptide-1 (GLP-1) is a 30-residue peptide hormone released from intestinal L cells following nutrient consumption. It is derived from proglucagon and exists in two equipotent biologically active forms: GLP-1 (7-36) amide and GLP-1 (7-37). Endogenous GLP-1 has a very short half-life (approx. 2 minutes) primarily due to degradation by DPP-4. GLP-1 functions by binding to the GLP-1 receptor (GLP-1R), a widely distributed class B GPCR. Its biological functions include potentiating glucose-induced insulin secretion (incretin effect), improving pancreatic beta-cell health and function, reducing glucagon secretion, delaying gastric emptying, promoting satiety, and affecting overall metabolic processes. Due to these beneficial effects, GLP-1 is a significant therapeutic target for type 2 diabetes and obesity. Treatment approaches include using long-lasting GLP-1 receptor agonists or inhibiting the enzyme (DPP-4) that degrades endogenous GLP-1.

Other names

GLP-1 (7-36) amideGLP-1 (7-37)Incretin hormone

GLP-1 exerts its effects by binding to the Glucagon-like peptide-1 receptor (GLP-1R), a class B G protein-coupled receptor. This binding triggers a signaling cascade involving the activation of a stimulatory G protein, adenylate cyclase, generation of cAMP, activation of protein kinase A (PKA) and cAMP-regulated guanine nucleotide exchange factor II (Epac2), leading to altered ion channel activity and elevation of intracellular calcium concentrations. Therapeutically, GLP-1 receptor agonists mimic this action by binding to GLP-1R, while DPP-4 inhibitors prevent the rapid degradation of endogenous GLP-1 by dipeptidyl peptidase-4 (DPP-4), increasing its half-life and activity.