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Metabolic Messengers: glucagon

Nature Metabolism volume 5, pages 186–192 (2023)Cite this article

Subjects

Abstract

Plasma glucose is tightly regulated via the secretion of the two glucose-regulating hormones insulin and glucagon. Situated next to the insulin-secreting β-cells, the α-cells produce and secrete glucagon—one of the body’s few blood glucose-increasing hormones. Diabetes is a bihormonal disorder, resulting from both inadequate insulin secretion and dysregulation of glucagon. The year 2023 marks the 100th anniversary of the discovery of glucagon, making it particularly timely to highlight the roles of this systemic metabolic messenger in health and disease.

Glucagon, secreted by the α-cells of the pancreatic islets of Langerhans, is one of the body’s principal hyperglycemic hormones, along with others such as adrenline1. Together with insulin, these hormones ensure that plasma glucose levels are kept within a narrow range, regardless of eating, exercise and fasting2. Glucagon mediates its action on hepatic glucose production via stimulation of glycogenolysis and gluconeogenesis. A fall in plasma glucose levels is perhaps the most well-known stimulus for increasing glucagon secretion, but it is also regulated by amino acids, fatty acids, neurotransmitters and circulating hormones3,4,5. Interest in the regulation of glucagon secretion has resurged, notably following the rediscovery of the central role of glucagon in diabetes6 and the recent discovery of its key role in systemic amino-acid metabolism7.

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Fig. 1: Timeline of important discoveries in glucagon research.
Fig. 2: Tissue regulation by glucagon.
Fig. 3: Regulation of glucagon secretion.

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Acknowledgements

P.E.M. holds the Canada Research Chair in Islet Biology and his work was funded by grants from the Canadian Institutes of Health Research (CIHR; FS 148451), the National Institutes of Health (NIH; R01DK126482; U01DK123716; U01DK120447) and CIHR/JDRF/Diabetes Canada (TG 179092; SRA-2021-1149-S-B). P.R.’s studies are supported by the RCUK Medical Research Council (MR/VO11979/1), The Leona M. and Harry B. Helmsley Charitable Trust (G-1912-03553 & G-2305-06047) and the Swedish Research Council (grant no: 2013-7107).

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Authors and Affiliations

  1. Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada

    Patrick E. MacDonald

  2. Department of Pharmacology, University of Alberta, Edmonton, AB, Canada

    Patrick E. MacDonald

  3. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK

    Patrik Rorsman

  4. Metabolic Physiology, Institute of Neuroscience and Physiology, University of Göteborg, Gothenburg, Sweden

    Patrik Rorsman

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MacDonald, P.E., Rorsman, P. Metabolic Messengers: glucagon. Nat Metab 5, 186–192 (2023). https://doi.org/10.1038/s42255-022-00725-3

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