Insulin-like peptide 5 is an orexigenic gastrointestinal hormone.

Johannes Grosse, Helen Heffron, Keith Burling, Mohammed Akhter Hossain, Abdella M Habib, Gareth J Rogers, Paul Richards, Rachel Larder, Debra Rimmington, Alice A Adriaenssens, Laura Parton, Justin Powell, Matteo Binda, William H Colledge, Joanne Doran, Yukio Toyoda, John D Wade, Samuel Aparicio, Mark B L Carlton, Anthony P Coll, Frank Reimann, Stephen O'Rahilly, Fiona M Gribble, Proceedings of the National Academy of Sciences of the United States of America 111, 11133-8 (2014)
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The gut endocrine system is emerging as a central player in the control of appetite and glucose homeostasis, and as a rich source of peptides with therapeutic potential in the field of diabetes and obesity. In this study we have explored the physiology of insulin-like peptide 5 (Insl5), which we identified as a product of colonic enteroendocrine L-cells, better known for their secretion of glucagon-like peptide-1 and peptideYY. i.p. Insl5 increased food intake in wild-type mice but not mice lacking the cognate receptor Rxfp4. Plasma Insl5 levels were elevated by fasting or prolonged calorie restriction, and declined with feeding. We conclude that Insl5 is an orexigenic hormone released from colonic L-cells, which promotes appetite during conditions of energy deprivation.