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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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Volume 47, Issue 3


Phenotyping of congenic dipeptidyl peptidase 4 (DP4) deficient Dark Agouti (DA) rats suggests involvement of DP4 in neuro-, endocrine, and immune functions

Nadine Frerker / Kerstin Raber
  • 2Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany and Experimental Therapy, Franz-Penzoldt-Center, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Felix Bode / Thomas Skripuletz / Heike Nave / Christian Klemann / Reinhard Pabst / Michael Stephan
  • 8Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany and Clinic for Psychosomatic and Psychotherapy, Hannover, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jutta Schade / Georg Brabant / Dirk Wedekind / Roland Jacobs / Anne Jörns / Ulf Forssmann / Rainer H. Straub / Sigrid Johannes / Torsten Hoffmann / Leona Wagner / Hans-Ulrich Demuth / Stephan von Hörsten
  • 20Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany and Experimental Therapy, Franz-Penzoldt-Center, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar


Background: Treatment of diabetes type 2 using chronic pharmacological inhibition of dipeptidyl peptidase 4 (DP4) still requires an in-depth analysis of models for chronic DP4 deficiency, because adverse reactions induced by some DP4 inhibitors have been described.

Methods: In the present study, a novel congenic rat model of DP4 deficiency on a “DP4-high” DA rat genetic background was generated (DA.F344-Dpp4m/SvH rats) and comprehensively phenotyped.

Results: Similar to chronic pharmacological inhibition of DP4, DP4 deficient rats exhibited a phenotype involving reduced diet-induced body weight gain and improved glucose tolerance associated with increased levels of glucagon-like peptide-1 (GLP-1) and bound leptin as well as decreased aminotransferases and triglycerides. Additionally, DA.F344-Dpp4m/SvH rats showed anxiolytic-like and reduced stress-like responses, a phenomenon presently not targeted by DP4 inhibitors. However, several immune alterations, such as differential leukocyte subset composition at baseline, blunted natural killer cell and T-cell functions, and altered cytokine levels were observed.

Conclusions: While this animal model confirms a critical role of DP4 in GLP-1-dependent glucose regulation, genetically induced chronic DP4 deficiency apparently also affects stress-regulatory and immune-regulatory systems, indicating that the use of chronic DP4 inhibitors might have the potential to interfere with central nervous system and immune functions in vivo.

Clin Chem Lab Med 2009;47:275–87.

Keywords: comprehensive phenotyping; dipeptidyl peptidase 4; inhibitors; neuropeptide Y

About the article

Corresponding author: Dr. Stephan von Hörsten, Experimental Therapy, Franz-Penzoldt-Center, Friedrich-Alexander-University Erlangen-Nürnberg, Palmsanlage 5, 91054 Erlangen, Germany Phone: +49-9131-8523504, Fax: +49-9131-8523502,

Received: 2008-11-10

Accepted: 2009-01-22

Published in Print: 2009-03-01

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 47, Issue 3, Pages 275–287, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2009.064.

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