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The metabolic actions of glucagon revisited

Abstract

The initial identification of glucagon as a counter-regulatory hormone to insulin revealed this hormone to be of largely singular physiological and pharmacological purpose. Glucagon agonism, however, has also been shown to exert effects on lipid metabolism, energy balance, body adipose tissue mass and food intake. The ability of glucagon to stimulate energy expenditure, along with its hypolipidemic and satiating effects, in particular, make this hormone an attractive pharmaceutical agent for the treatment of dyslipidemia and obesity. Studies that describe novel preclinical applications of glucagon, alone and in concert with glucagon-like peptide 1 agonism, have revealed potential benefits of glucagon agonism in the treatment of the metabolic syndrome. Collectively, these observations challenge us to thoroughly investigate the physiology and therapeutic potential of insulin's long-known opponent.

Key Points

  • In addition to its well-known effects on glycemia, increased glucagon signaling directly regulates triglyceride, free fatty acid, apolipoprotein and bile acid metabolism

  • Glucagon action can be inhibited via receptor desensitization by excess dietary fat intake

  • Energy expenditure and thermogenesis are increased by glucagon agonism

  • Glucagon administration stimulates satiety and decreases food intake

  • Glucagon action, in combination with incretins such as glucagon-like peptide 1, may be a crucial tool in the treatment of the metabolic syndrome

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All authors researched the data for the article, provided a substantial contribution to discussions of the content, contributed equally to writing the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Matthias H. Tschöp.

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N. Geary declares an association with the following company: Novo Nordisk (consultant). R. DiMarchi declares an association with the following company: Marcadia Biotech (stockholder/director). The other authors declare no competing interests.

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Habegger, K., Heppner, K., Geary, N. et al. The metabolic actions of glucagon revisited. Nat Rev Endocrinol 6, 689–697 (2010). https://doi.org/10.1038/nrendo.2010.187

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