Research from the Gribble-Reimann group and published this week in Cell Reports has demonstrated the ability to label and maintain fully functional human L-cells in organoid culture. This opens opportunities to explore L-cell function and develop drugs targeting the human enteroendocrine system.

Enteroendocrine cells (EECs) produce a range of gut hormones that have key roles in the coordination of food digestion and absorption, insulin secretion and appetite. The gut hormone, glucagon-like peptide-1 (GLP-1) from L-cells in the intestine, stimulates insulin secretion and reduces appetite after food ingestion, and it is the basis for a number of widely-used drugs against type-2 diabetes and obesity, as well as many more in the pipeline. Drugs directly targeting L- and other enteroendocrine cells are under development, with the aim of mimicking the endocrine effects of gastric bypass surgery, but they are difficult to develop without human L-cell models.

The application of methods demonstrated here to organoids from other regions of the human gastrointestinal tract, combined with the harnessing of different gut hormonal promoters, will in future enable characterization of the full range of human EEC types, and facilitate screening for drugs that increase gut hormone secretion for the treatment of metabolic diseases.