Gut hormones orchestrate pivotal physiological processes in multiple metabolically active tissues, including the pancreas, liver, adipose tissue, gut and central nervous system, making them attractive therapeutic targets in the treatment of obesity and type 2 diabetes mellitus. Most gut hormones are derived from enteroendocrine cells, but bioactive peptides that are derived from other intestinal epithelial cell types have also been implicated in metabolic regulation and can be considered gut hormones. A deeper understanding of the complex inter-organ crosstalk mediated by the intestinal endocrine system is a prerequisite for designing more effective drugs that are based on or target gut hormones and their receptors, and extending their therapeutic potential beyond obesity and diabetes mellitus. In this Review, we present an overview of gut hormones that are involved in the regulation of metabolism and discuss their action in the gastrointestinal system and beyond.
The gastrointestinal tract acts as a major endocrine organ, releasing various gut hormones that regulate physiological functions such as nutrient absorption, insulin release and appetite.
Gut hormones are produced by a variety of enteroendocrine cells (EECs) and non-enteroendocrine cells, which respond differently to different stimuli and secrete specific combinations of hormones.
EECs sense varied nutritional and non-nutritional stimuli via an array of sensory transporters, ion channels and receptors, making them an effective link between nutrient absorption and gut hormonal responses.
The biosynthesis and release pathways of gut hormones that are derived from cells other than EECs are poorly understood and are a potential area for further research.
A comprehensive understanding of gut hormones, their interactions with other organs and their complex regulatory mechanisms could help to identify new therapeutic modalities and extend the therapeutic potential of gut hormones.
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Research in the laboratories of F.R. and F.M.G. is supported by the Medical Research Council (MRC_MC_UU_12012/3) and the Wellcome Trust (220271/Z/20/Z).
The laboratory of F.R. currently hosts projects that receive funding from AstraZeneca, Eli Lilly and LGC Group. The laboratory of F.M.G. currently hosts projects that receive funding from AstraZeneca, Eli Lilly and LGC Group. R.B.B. declares no competing interests.
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Bany Bakar, R., Reimann, F. & Gribble, F.M. The intestine as an endocrine organ and the role of gut hormones in metabolic regulation. Nat Rev Gastroenterol Hepatol 20, 784–796 (2023). https://doi.org/10.1038/s41575-023-00830-y