Glucagon induces the hepatic expression of inflammatory markers in vitro and in vivo

Glucagon exerts multiple hepatic actions, including stimulation of glycogenolysis/gluconeogenesis. The liver plays a crucial role in chronic inflammation by synthesizing proinflammatory molecules, which are thought to contribute to insulin resistance and hyperglycaemia. Whether glucagon affects hepatic expression of proinflammatory cytokines and acute‐phase reactants is unknown. Herein, we report a positive relationship between fasting glucagon levels and circulating interleukin (IL)‐1β (r = 0.252, p = .042), IL‐6 (r = 0.230, p = .026), fibrinogen (r = 0.193, p = .031), complement component 3 (r = 0.227, p = .024) and high sensitivity C‐reactive protein (r = 0.230, p = .012) in individuals without diabetes. In CD1 mice, 4‐week continuous treatment with glucagon induced a significant increase in circulating IL‐1β (p = .02), and IL‐6 (p = .001), which was countered by the contingent administration of the glucagon receptor antagonist, GRA‐II. Consistent with these results, we detected a significant increase in the hepatic activation of inflammatory pathways, such as expression of NLRP3 (p