Effects of dipeptidyl peptidase IV on the satiety actions of peptide YY. 2006

S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
Laboratory of Cellular and Molecular Medicine, Departments of Cellular and Physiological Sciences and Surgery, Life Sciences Institute, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3 Canada.

OBJECTIVE 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). 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 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.

UI MeSH Term Description Entries
D007263 Infusions, Parenteral The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping. Intra-Abdominal Infusions,Intraperitoneal Infusions,Parenteral Infusions,Peritoneal Infusions,Infusion, Intra-Abdominal,Infusion, Intraperitoneal,Infusion, Parenteral,Infusion, Peritoneal,Infusions, Intra-Abdominal,Infusions, Intraperitoneal,Infusions, Peritoneal,Intra Abdominal Infusions,Intra-Abdominal Infusion,Intraperitoneal Infusion,Parenteral Infusion,Peritoneal Infusion
D007700 Kinetics The rate dynamics in chemical or physical systems.
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012528 Satiety Response Behavioral response associated with the achieving of gratification. Response, Satiety,Responses, Satiety,Satiety Responses
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018819 Dipeptidyl Peptidase 4 A serine protease that catalyses the release of an N-terminal dipeptide. Several biologically-active peptides have been identified as dipeptidyl peptidase 4 substrates including INCRETINS; NEUROPEPTIDES; and CHEMOKINES. The protein is also found bound to ADENOSINE DEAMINASE on the T-CELL surface and is believed to play a role in T-cell activation. Antigens, CD26,CD26 Antigens,Dipeptidyl-Peptidase IV,Adenosine Deaminase Complexing Protein 2,CD26 Antigen,Antigen, CD26,Dipeptidyl Peptidase IV
D019894 Peptide YY A 36-amino acid peptide produced by the L cells of the distal small intestine and colon. Peptide YY inhibits gastric and pancreatic secretion. PYY Peptide,Peptide, PYY

Related Publications

S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
December 1993, Regulatory peptides,
S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
January 2010, Journal of pediatric endocrinology & metabolism : JPEM,
S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
January 2015, Food & function,
S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
February 1985, Biological chemistry Hoppe-Seyler,
S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
June 2002, IDrugs : the investigational drugs journal,
S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
January 2008, Clinical and experimental pharmacology & physiology,
S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
May 1991, Biological chemistry Hoppe-Seyler,
S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
January 2006, Advances in experimental medicine and biology,
S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
January 1978, Acta biologica et medica Germanica,
S Unniappan, and C H S McIntosh, and H-U Demuth, and U Heiser, and R Wolf, and T J Kieffer
January 1997, Journal of enzyme inhibition,
Copied contents to your clipboard!