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Biomark Med. 2016 Nov;10(11):1141-1151. Epub 2016 Sep 9.

The biology of glucagon and the consequences of hyperglucagonemia.

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Department of Biomedical Sciences, Faculty of Health & Medical Sciences, University of Copenhagen, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health & Medical Sciences, University of Copenhagen, Denmark.
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.


The proglucagon-derived peptide hormone, glucagon, comprises 29 amino acids. Its secretion from the pancreatic α cells is regulated by several factors. Glucagon increases blood glucose levels through gluconeogenesis and glycogenolysis. Elevated plasma concentrations of glucagon, hyperglucagonemia, may contribute to diabetes. However, hyperglucagonemia is also observed in other clinical conditions than diabetes, including nonalcoholic fatty liver disease, glucagon-producing tumors and after gastric bypass surgery. Here, we review the current literature on hyperglucagonemia in disease with a particular focus on diabetes, and finally speculate that the primary physiological importance of glucagon may not reside in glucose homeostasis but in regulation of amino acid metabolism exerted via a hitherto unrecognized hepato-pancreatic feedback loop.


diabetes; glucagon; hyperglucagonemia; proglucagon

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