The intestine as an endocrine organ and the role of gut hormones in metabolic regulation

Bany Bakar, Rula; Reimann, Frank; Gribble, Fiona M.

doi:10.1038/s41575-023-00830-y

Cited by 39 publications

(13 citation statements)

References 213 publications

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“…16,26 However, many hormone pairs have opposing effects, for example on appetite, exocrine pancreas stimulation, or glycemia. 8,14 It is therefore important that any EEC tailor its hormonal repertoire to match its environmental sensors and secretory capacity; moreover, TPH1 and other transcripts are exquisitely restricted to EC, which are unambiguously distinct from non-EC, cells. Compared to cells treated with a non-specific gRNA, our findings implicate ASCL1 , HES6 and NEUROD1 in EEC fidelity, with ASCL1 and NEUROD1 losses showing opposite effects on EC vs. non-EC character and HES6 and ASCL1 losses showing opposite effects on X- vs. D-cell character.…”

Section: Discussionmentioning

confidence: 99%

“…Congenital EEC deficits are life-threatening in humans 10 and mice; 11 conversely, EEC properties can be harnessed by reprogramming, for example to secrete insulin and control hyperglycemia. 12,13 EECs divide broadly into enterochromaffin (EC) cells, which secrete 5-hydroxytryptamine (5HT, serotonin) and various non-EC cells, each of which produces a dominant or at most a few of the >20 known enteric peptide hormones, 14 such as glucagon-like peptide 1 (GLP-1 – an incretin), ghrelin (GHRL – an orexigen) or somatostatin (SST – an antagonist of many hormones); GLP-1 agonists are used to treat type 2 diabetes and obesity. 8 Because EECs sense and respond to local signals and many peptide hormones oppose one another, limiting the array of hormones in any EEC is a physiologic adaptation.…”

Section: Introductionmentioning

confidence: 99%

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Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation

Singh,

Gu,

Madha

et al. 2024

Preprint

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Enteroendocrine cells (EECs), which secrete serotonin (enterochromaffin cells, EC) or a dominant peptide hormone, serve vital physiologic functions. As with any adult human lineage, the basis for terminal cell diversity remains obscure. We replicated human EEC differentiation in vitro, mapped transcriptional and chromatin dynamics that culminate in discrete cell types, and studied abundant EEC precursors expressing selected transcription factors (TFs) and gene programs. Before expressing the pre-terminal factor NEUROD1, non-replicating precursors oscillated between epigenetically similar but transcriptionally distinct ASCL1+ and HES6hi cell states. Loss of either factor substantially accelerated EEC differentiation and disrupted EEC individuality; ASCL1 or NEUROD1 deficiency had opposing consequences on EC and hormone- producing cell features. Expressed late in EEC differentiation, the latter TFs mainly bind cis- elements that are accessible in undifferentiated stem cells and tailor the subsequent expression of TF combinations that specify EEC types. Thus, TF oscillations retard EEC maturation to enable accurate EEC diversification.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation

Singh,

Gu,

Madha

et al. 2024

Preprint

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“…Enteric secretin refers to a class of hormones secreted by intestinal endocrine cells, such as glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), and vasoactive enteropeptide (VIP). These hormones are produced by EECs, including L-cells, K-cells, and I-cells found in the ileum and colon ( Bany Bakar et al, 2023 ). The release of intestinal secretin is regulated by several factors, among which mechanical stimulation is an important regulatory factor that can activate neurons or act directly on endocrine cells, thereby stimulating or inhibiting the release of intestinal secretin ( Treichel et al, 2018 ; Joshi et al, 2021 ).…”

Section: Physiological Roles Of Piezo Channels In the Gi Tractmentioning

confidence: 99%

Piezo channels in the intestinal tract

He,

Zhou,

et al. 2024

Front. Physiol.

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The intestine is the largest mechanosensitive organ in the human body whose epithelial cells, smooth muscle cells, neurons and enteroendocrine cells must sense and respond to various mechanical stimuli such as motility, distension, stretch and shear to regulate physiological processes including digestion, absorption, secretion, motility and immunity. Piezo channels are a newly discovered class of mechanosensitive ion channels consisting of two subtypes, Piezo1 and Piezo2. Piezo channels are widely expressed in the intestine and are involved in physiological and pathological processes. The present review summarizes the current research progress on the expression, function and regulation of Piezo channels in the intestine, with the aim of providing a reference for the future development of therapeutic strategies targeting Piezo channels.

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“…In recent years, the interplay between the digestive system and disc homeostasis has received increasing attention, with a special focus on the role of the gut microbiota in the gastrointestinal endocrine system ( 150 – 153 ). It is worth noting that the endocrine functions of the digestive system facilitate complex inter-organ communication through various gastrointestinal hormones (such as Ghrelin and Amylin) and hepatokines ( Figure 4 , Table 3 ) ( 154 , 155 ). Insight into how these endocrine factors influence disc physiology can expand our understanding of IVDD.…”

Section: Gastrointestinal Hormones and Hepatokinesmentioning

confidence: 99%

Roles of organokines in intervertebral disc homeostasis and degeneration

He,

Liu,

Lin

et al. 2024

Front. Endocrinol.

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The intervertebral disc is not isolated from other tissues. Recently, abundant research has linked intervertebral disc homeostasis and degeneration to various systemic diseases, including obesity, metabolic syndrome, and diabetes. Organokines are a group of diverse factors named for the tissue of origin, including adipokines, osteokines, myokines, cardiokines, gastrointestinal hormones, and hepatokines. Through endocrine, paracrine, and autocrine mechanisms, organokines modulate energy homeostasis, oxidative stress, and metabolic balance in various tissues to mediate cross-organ communication. These molecules are involved in the regulation of cellular behavior, inflammation, and matrix metabolism under physiological and pathological conditions. In this review, we aimed to summarize the impact of organokines on disc homeostasis and degeneration and the underlying signaling mechanism. We focused on the regulatory mechanisms of organokines to provide a basis for the development of early diagnostic and therapeutic strategies for disc degeneration.

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The intestine as an endocrine organ and the role of gut hormones in metabolic regulation

Cited by 39 publications

References 213 publications

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation

Piezo channels in the intestinal tract

Roles of organokines in intervertebral disc homeostasis and degeneration

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