Glucagon-like peptide-1 (GLP-1), secreted by intestinal L-cells after a meal, stimulates insulin secretion via a mechanism that is distinct from nutrient-stimulated insulin release. The primary intracellular pathway activated by GLP-1 in beta cells is:

• A GLP-1 receptor → Gs → cAMP → PKA + EPAC2 → enhanced Ca²⁺ release and granule exocytosis ✓
• B GLP-1 receptor → Gq → IP3 → ER Ca²⁺ release → insulin exocytosis
• C GLP-1 receptor → JAK-STAT → IRS-1 phosphorylation → PI3K → Akt-mediated exocytosis
• D GLP-1 receptor → KATP channel closure → depolarisation → Ca²⁺ entry (same as glucose pathway)

Explanation

GLP-1 binds its Gs-coupled receptor on beta cells, raising intracellular cAMP. Elevated cAMP activates both protein kinase A (PKA) and the exchange protein EPAC2 (also called cAMP-GEFII). PKA phosphorylates components of the exocytotic machinery, while EPAC2 directly potentiates Ca²⁺-triggered granule fusion. This pathway amplifies insulin release triggered by glucose-KATP channel closure — a critical concept in the 'incretin effect'. GLP-1 receptor agonists (liraglutide, semaglutide) exploit this mechanism therapeutically.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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