Glucagon's yin and yang effects on hepatic glucose production

Abstract

New insights into the actions of the hormone glucagon are provided by a recent study in rodents, which shows that glucagon can suppress hepatic glucose production by acting through the mediobasal hypothalamic region of the brain. This central regulatory mechanism is impaired in rats fed a high-fat diet, suggesting that hypothalamic glucagon resistance may be relevant to the hyperglycemia observed in obesity, diabetes or both (pages 766–772).

Figure 1

Glucagon infusion rapidly stimulates hepatic glucose production, but the effect wanes with time. New data from Mighiu et al. indicate that glucagon action in the MBH can inhibit glucose production in rodents and that this neural circuit contributes to the evanescence of glucagon’s direct hepatic effect. Feeding rats a high-fat diet results in MBH glucagon resistance, suggesting that impairment of this negative feedback loop may contribute to hyperglycemia in obesity, diabetes or both.