{
  "abstract": "Intestinal enteroendocrine L-cells play a central role in metabolic homeostasis by secreting the gut hormones GLP-1 and PYY, but whether and how neural signals regulate human L-cell function remains poorly understood. This gap reflects the limited availability of human model systems enriched for mature L-cells. Here, we establish a differentiation strategy that generates human donor-derived ileal organoids with markedly increased L-cell abundance, enabling functional interrogation of L-cell physiology in their basal state. Using this system, we show that cholinergic and adrenergic stimuli activate L-cells, triggering calcium influx and secretion of GLP-1 and PYY. Pharmacological analysis reveals that cholinergic regulation of human L-cells is mediated predominantly through M3 muscarinic receptors, while adrenergic regulation is mediated through the {beta}1 adrenergic receptor. Neurotransmitter-evoked activation also initiates gap junction-dependent calcium waves that propagate across the intestinal epithelium; however, disruption of epithelial coupling by abolishing calcium propagation does not impair hormone secretion. Together, these findings identify L-cells as integrative hubs that couple neural signals to gut hormone secretion and epithelial calcium waves, providing mechanistic insight into the gut-brain axis and how the nervous system regulates intestinal endocrine function in human intestine.",
  "abstract_shown": true,
  "affiliations": [
    "Wyss Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "J. Lindsay"
    },
    {
      "name": "D. Zeve"
    },
    {
      "name": "S. Rudolph"
    },
    {
      "name": "A. Shepherd"
    },
    {
      "name": "A. Grossberg"
    },
    {
      "name": "D. Breault"
    },
    {
      "name": "M. Levin"
    },
    {
      "affs": [
        0
      ],
      "name": "D. Ingber"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bhtcwwdfyg8zs.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.03.763680",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763680v1.full",
  "id": "bhtcwwdfyg8zs",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763680v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763680v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bhtcwwdfyg8zs.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:21:07Z",
      "native_id": "10.64898/2026.11.03.763680",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763680v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Neural Activation of Human Primary Intestinal Enteroendocrine L-cells",
  "title_text": "Neural Activation of Human Primary Intestinal Enteroendocrine L-cells",
  "type": "preprint",
  "updated_at": "2026-11-06T00:21:07Z",
  "url": "https://research.draconitic.com/paper/bhtcwwdfyg8zs",
  "venue": "bioRxiv",
  "versions": []
}