Insulin-like peptide 5 is an orexigenic gastrointestinal hormone

Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11133-8. doi: 10.1073/pnas.1411413111. Epub 2014 Jul 15.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colon / metabolism*
  • Eating / drug effects*
  • Eating / physiology*
  • Enteroendocrine Cells / metabolism*
  • Female
  • Glucagon-Like Peptide 1 / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Peptide Hormones / metabolism*
  • Peptide Hormones / pharmacology*
  • Peptide YY / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Peptide / metabolism


  • Insl5 protein, mouse
  • Peptide Hormones
  • RXFP4 protein, human
  • RXFP4 protein, mouse
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • Peptide YY
  • Glucagon-Like Peptide 1