Insulin-like peptide 5 is an orexigenic gastrointestinal hormone

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 ide...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2014-07, Vol.111 (30), p.11133-11138
Main Authors: Grosse, Johannes, Heffron, Helen, Burling, Keith, Hossain, Mohammed Akhter, Habib, Abdella M., Rogers, Gareth J., Richards, Paul, Larder, Rachel, Rimmington, Debra, Adriaenssens, Alice A., Parton, Laura, Powell, Justin, Binda, Matteo, Colledge, William H., Doran, Joanne, Toyoda, Yukio, Wade, John D., Aparicio, Samuel, Carlton, Mark B. L., Coll, Anthony P., Reimann, Frank, O'Rahilly, Stephen, Gribble, Fiona M.
Format: Article
Language:English
Subjects:
Animals
Antibodies
Appetite
Biological Sciences
Body weight
Cells
Colon
Colon - metabolism
diabetes
Eating - drug effects
Eating - physiology
endocrine system
energy deprivation
Enteroendocrine cells
Enteroendocrine Cells - metabolism
fasting
Female
Food intake
gastrointestinal system
glucagon-like peptide 1
Glucagon-Like Peptide 1 - metabolism
Glucose
Homeostasis
Hormones
Humans
L cells
low calorie diet
Male
Mice
Mice, Knockout
Obesity
Peptide Hormones - metabolism
Peptide Hormones - pharmacology
Peptide YY - metabolism
Peptides
Receptors
Receptors, G-Protein-Coupled - metabolism
Receptors, Peptide - metabolism
Refeeding
Rodents
secretion
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1411413111