Peptide directoryGut, pancreas & liver

Insulin-like peptide 5

A colon hormone of the insulin family that rises with fasting.

Where it comes from

Made in
L cells of the colon and rectum, the same cells that make GLP-1 and PYY
Sent out by
Fasting and calorie restriction raise it; feeding lowers it
Acts on
  • Hypothalamus
  • Pancreatic islets
  • Colon

What it does

  • Reported to make mice eat more, the first gut hormone said to drive hunger rather than fullness 1
  • A later study in obese mice found no effect on food intake, body weight or glucose handling 2
  • Promotes insulin release in some preparations, and its role in people is open

In medicine

  • None: no medicine, and no clinical assay measures it
  • It is hard to measure at all. The peptide has two chains and three disulfide bonds, circulates in tiny amounts and is almost absent from human blood in some studies, which is part of why the human picture is thin 2

Beyond the body’s own use

  • RXFP4 agonists and blockers exist as research tools and nothing is in human trials. A blocker would be the obesity candidate, if the orexigenic claim held
  • That claim is the unresolved part. The 2014 work rested on gene-deleted mice and on injections of the peptide 1; the 2019 work used a stabilised analogue in diet-induced obese mice and saw nothing 2, and the two have not been reconciled

Sources

  1. Grosse et al., Insulin-like peptide 5 is an orexigenic gastrointestinal hormone, Proceedings of the National Academy of Sciences 2014
  2. Zaykov et al., Insulin-like peptide 5 fails to improve metabolism or body weight in obese mice, Peptides 2019

This card describes what a medicine is for and what the evidence says; it recommends nothing. Talk to your clinician about anything you read here.