A patient with type 2 diabetes and obesity is commenced on a GLP-1 receptor agonist. Which statement correctly describes the mechanism of glucose-dependent insulin secretion by this drug class?
- A They directly open beta-cell ATP-sensitive K+ channels causing insulin exocytosis
- B GLP-1 receptor agonists stimulate insulin release via Gs/cAMP/PKA pathway only in the presence of glucose, preventing hypoglycaemia at low plasma glucose levels ✓
- C They inhibit DPP-4, prolonging endogenous GLP-1 half-life
- D They activate PPAR-gamma receptors to enhance insulin sensitivity
Explanation
GLP-1 receptor agonists bind Gs-coupled GLP-1 receptors on pancreatic beta cells, raising cAMP and activating PKA/Epac2, which potentiates glucose-induced insulin secretion. Critically, this signalling cascade only amplifies insulin release when intracellular glucose metabolism is actively generating ATP — when plasma glucose is low, there is insufficient basal stimulation for hypoglycaemia. This glucose-dependence is the major safety advantage over sulfonylureas. DPP-4 inhibition is the mechanism of gliptins; PPAR-gamma activation is the mechanism of thiazolidinediones.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.