Fig. 2: Mechanism of action of GLP-1.
From: Designing GLP-1 delivery: structural perspectives and formulation approaches for optimized therapy
This figure delineates the molecular signaling mechanism activated by glucagon-like peptide-1 (GLP-1) in pancreatic β cells. Binding of GLP-1 to its receptor initiates G-protein activation, leading to stimulation of adenylyl cyclase and subsequent elevation of intracellular cyclic AMP (cAMP) levels. Increased cAMP activates protein kinase A (PKA), which, alongside CaMKIV, phosphorylates CREB to promote insulin gene transcription. Simultaneously, PKA triggers membrane depolarization and opens voltage-gated Ca²⁺ channels, elevating cytosolic Ca²⁺ concentrations. The rise in Ca²⁺ is a critical signal that facilitates exocytosis of insulin granules, coupling GLP-1 receptor activation to enhanced insulin secretion and synthesis.
