Neural Activation of Human Primary Intestinal Enteroendocrine L-cells

Cholinergic and adrenergic stimulation activates human ileal organoid–derived enteroendocrine L-cells, producing calcium influx and secretion of GLP-1 and PYY.

• Why it matters: Neural control of human L-cell physiology is unclear, partly because mature L-cell–enriched human model systems have been limited.
• What they did: Human donor-derived ileal organoids were differentiated to markedly increase L-cell abundance, then exposed to cholinergic and adrenergic stimuli with calcium imaging and hormone readouts.
• The result: Cholinergic effects are mediated predominantly by M3 muscarinic receptors and adrenergic effects by the {beta}1 adrenergic receptor; neurotransmitter-evoked calcium waves depend on gap junctions, yet blocking calcium propagation does not impair hormone secretion.

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