Motilin: a panoply of communications between the gut, brain, and pancreas

Introduction: Motilin was first alluded to nearly a century ago. But it remains a rather abstruse peptide, in the shadow of its younger but more lucid 'cousin' ghrelin.Areas covered: The review aimed to bring to the fore multifarious aspects of motilin research with a view to aiding prioritization of future studies on this gastrointestinal peptide.Expert opinion: Growing evidence indicates that rodents (mice, rats, guinea pigs) do not have functional motilin system and, hence, studies in these species are likely to have a minimal translational impact. Both the active peptide and motilin receptor were initially localized to the upper gastrointestinal tract only but more recently – also to the brain (in both humans and other mammals with functional motilin system). Motilin is now indisputably implicated in interdigestive contractile activity of the gastrointestinal tract (in particular, gastric phase III of the migrating motor complex). Beyond this role, evidence is building that there is a cross-talk between motilin system and the brain-pancreas axis, suggesting that motilin exerts not only contractile but also orexigenic and insulin secretagogue actions.