Gcgr−/− mice lack functional glucagon receptors. [125I]Glucagon-binding (a) and glucagon-stimulated cAMP production (b) in liver membranes from male Gcgr+/+, Gcgr+/−, and Gcgr−/− mice. Control (open bars), Gcgr+/− (hatched bars), and Gcgr−/− (filled bars) mice are indicated. Gluc, glucagon; Forsk, forskolin. Data represent mean ± SEM (n = 3) from three independent preparations. (c) Intraperitoneal glucagon challenge of male Gcgr−/− (●), Gcgr+/− (▴), and Gcgr+/+ (□) mice. Data represent mean ± SEM, n = 5–7. *, P < 0.05; **, P < 0.01; ***, P < 0.001.