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Both receptor subtypes signal primarily via Gαs → adenylyl cyclase → cAMP, but their tissue distribution and downstream metabolic effects differ critically: GLP-1R activation drives pancreatic insulin secretion, hypothalamic satiety signalling, and gastric emptying inhibition, while GCGR activation stimulates hepatic fatty acid β-oxidation, suppresses hepatic lipogenesis, and upregulates thermogenic pathways — making GCGR engagement a subject of strong research interest in models of hepatic steatosis and metabolic dysfunction-associated steatohepatitis (MASH)

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Bettoli V, Zauli S, Montis A, Ruina G, Virgili A