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  • Review Article
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Ghrelin, the proglucagon-derived peptides and peptide YY in nutrient homeostasis

Nature Reviews Gastroenterology & Hepatology volume 9, pages 705–715 (2012)Cite this article

Subjects

Abstract

Dysregulation of nutrient homeostasis is implicated in the current epidemics of obesity and type 2 diabetes mellitus. The maintenance of homeostasis in the setting of repeated cycles of feeding and fasting occurs through complex interactions between metabolic, hormonal and neural factors. Although pancreatic islets, the liver, muscle, adipocytes and the central nervous system are all key players in this network, the gastrointestinal tract is the first tissue exposed to ingested nutrients and thus has an important role. This Review focuses on several of the endocrine hormones released by the gastrointestinal tract prior to or during nutrient ingestion that have key roles in maintaining energy balance. These hormones include the gastric orexigenic hormone, ghrelin, and the distal L cell anorexigenic and metabolic hormones, glucagon-like peptide (GLP)-1, GLP-2, oxyntomodulin and peptide YY. Each of these hormones exerts a distinct set of biological actions to maintain nutrient homeostasis, the properties of which are currently, or might soon be, exploited in the clinic for the treatment of obesity and type 2 diabetes mellitus.

Key Points

  • Enteroendocrine cells in the gastrointestinal tract produce various hormones that have essential roles in the maintenance of nutrient homeostasis in both the fasting and fed states

  • Ghrelin is an orexigenic peptide released by the proximal X/A-like cells prior to nutrient ingestion; the enteroendocrine L cells release glucagon-like peptide (GLP)-1, GLP-2, oxyntomodulin and peptide YY (PYY) in response to nutrient ingestion

  • GLP-1 is a key incretin hormone, which also inhibits glucagon release, gastric emptying and appetite; agents that increase GLP-1 action are used to treat type 2 diabetes mellitus

  • GLP-2 regulates nutrient absorption by the gastrointestinal tract through enhancement of intestinal growth, nutrient digestion and transport, as well as blood flow

  • The physiologic role of oxyntomodulin remains to be established, but exogenous administration suppresses food intake; PYY3–36NH2 has an important role as an anorexigenic gut hormone

  • Surgically induced alterations in the levels of ghrelin and/or GLP-1, oxyntomodulin and PYY improve glycaemic control and induce weight loss; pharmacological manipulation of these gut hormones might prove beneficial

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Figure 1: The X/A-like cell.
Figure 2: The L cell.

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Acknowledgements

C. X. Dong is supported by a graduate studentship from the Banting and Best Diabetes Centre, University of Toronto, Canada. P. L. Brubaker is supported by the Canada Research Chairs program. Studies on GLP-1 and GLP-2 in the Brubaker laboratory are supported by operating grants from the Canadian Diabetes Association (#2374) and the Canadian Institutes of Health Research (#MOP-9940), respectively.

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    Charlotte X. Dong & Patricia L. Brubaker

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C. X. Dong declares no competing interests. P. L. Brubaker has re-ceived consulting fees from Eli Lilly; Merck, Sharp & Dome; and NPS Pharmaceuticals.

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Dong, C., Brubaker, P. Ghrelin, the proglucagon-derived peptides and peptide YY in nutrient homeostasis. Nat Rev Gastroenterol Hepatol 9, 705–715 (2012). https://doi.org/10.1038/nrgastro.2012.185

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