Effects of dipeptidyl peptidase IV on the satiety actions of peptide YY.

Abstract

AIMS/HYPOTHESIS:

Dipeptidyl peptidase IV (DP IV) inhibitors are currently being developed to prolong the biological activity of insulinotropic peptides as a novel approach in the treatment of diabetes. We hypothesised that DP IV inhibition could attenuate the satiety actions of peptide YY (PYY) by altering the conversion of PYY(1-36) to PYY(3-36).

MATERIALS AND METHODS:

The effects of PYY delivered by osmotic mini-pumps were assessed in rats treated with a DP IV inhibitor and in a rat model deficient in DP IV.

RESULTS:

Pharmacological levels of total PYY were found in the circulation after the exogenous administration of PYY(3-36). While both PYY(1-36) and PYY(3-36) reduced food intake in normal rats, PYY(1-36) was ineffective in rats deficient in DP IV. When re-fed after a 24-h fast, DP IV-deficient rats exhibited higher food intake and weight gain than normal rats. Moreover, unlike controls, there was no postprandial increase in PYY levels in DP IV-deficient rats. Despite these findings, administration of a DP IV inhibitor, Pro-boroPro, did not alter the acute anorectic effects of exogenous PYY(1-36) in normal rats. This could be the result of the protection of other appetite regulatory peptides or the generation of PYY(3-36) by remaining DP IV activity or other dipeptidyl peptidases.

CONCLUSIONS/INTERPRETATION:

Although DP IV inhibition with Pro-boroPro attenuated the generation of PYY(3-36), our results indicate that short-term DP IV inhibition does not eliminate the satiety actions of exogenously administered PYY(1-36) at the doses tested.

• Authors: S Unniappan, C H S McIntosh, H-U Demuth, U Heiser, R Wolf, T J Kieffer
• Journal: Diabetologia (Diabetologia) Vol. 49 Issue 8 Pg. 1915-23 (Aug 2006) ISSN: 0012-186X [Print] Germany
• PMID: 16802131 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protease Inhibitors
• Peptide YY
• Dipeptidyl Peptidase 4

Topics

• Animals
• Dipeptidyl Peptidase 4 (metabolism)
• Humans
• Infusions, Parenteral
• Kinetics
• Peptide YY (administration & dosage, blood, pharmacology)
• Protease Inhibitors (pharmacology)
• Rats
• Rats, Inbred F344
• Satiety Response (drug effects, physiology)