How do you work out what stimulates release of a hormone which isn’t expressed in rodents or cell lines, and is challenging to measure reliably? Using newly-developed human small intestinal organoid lines and a targeted mass spectrometry assay, a recent study from the Gribble-Reimann laboratory at the IMS-MRL and published in Molecular Metabolism, presents the first detailed characterisation of the factors regulating secretion of the gut hormone motilin (MLN).
Motilin is an important regulator of gastrointestinal motility, and partly underlies the link between hunger and a ‘rumbly tummy’ (strong stomach contractions, known as phase III of the migrating motor complex). Between meals, motilin is released cyclically in response to duodenal acidification and gallbladder emptying. In this study, researchers identified acid-sensing ion channels (ASICs) and the G-protein bile acid receptor GPBAR1 as being at least partly responsible for this inter-digestive control of motilin secretion. Postprandial alterations in motilin are highly dependent on the meal’s macronutrient composition. Fats, however, appear to stimulate motilin release in human subjects, which researchers here showed is likely to occur by sensing of both lipid breakdown products – via the free fatty acid receptor FFA1 and monoacylglycerol receptor GPR119 – and bile acids acting on GPBAR1.
This work using organoids as an in vitro model of human enteroendocrine cell function offers new insights into the physiology of motilin, which is a potential target in the development of new prokinetic drugs.