Jump to ContentJump to Main Navigation
Show Summary Details
More options …

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

Online
ISSN
1437-4331
See all formats and pricing
More options …
Volume 47, Issue 3

Issues

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

Abstract

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.

Export Citation

©2009 by Walter de Gruyter Berlin New York.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Camilla Kienast, Hanns-Christian Gunga, and Mathias Steinach
REACH, 2019, Volume 14-15, Page 100032
[2]
Shian-Ren Lin, Chia-Hsiang Chang, May-Jwan Tsai, Henrich Cheng, Jian-Chyi Chen, Max K. Leong, and Ching-Feng Weng
Therapeutic Advances in Chronic Disease, 2019, Volume 10, Page 204062231987530
[3]
Sarah E. Herlihy, Darrell Pilling, Anu S. Maharjan, and Richard H. Gomer
The Journal of Immunology, 2013, Volume 190, Number 12, Page 6468
[4]
Claire Emson, Tuyet-Hang Pham, Scott Manetz, and Paul Newbold
Immunology and Allergy Clinics of North America, 2018
[5]
Yulia Golub, Eva-Maria Schildbach, Chadi Touma, Oliver Kratz, Gunther H. Moll, Stephan von Hörsten, and Fabio Canneva
Behavioural Brain Research, 2018
[6]
Eugene A. Zubkov, Yana A. Zorkina, Elena V. Orshanskaya, Nadezhda N. Khlebnikova, Natalia A. Krupina, and Vladimir P. Chekhonin
Neuropsychobiology, 2017, Volume 76, Number 2, Page 89
[7]
Anne-Christine Plank, Fabio Canneva, Kerstin A. Raber, Yvonne K. Urbach, Julia Dobner, Maja Puchades, Jan G. Bjaalie, Clarissa Gillmann, Tobias Bäuerle, Olaf Riess, Hoa H. P. Nguyen, and Stephan von Hörsten
Frontiers in Neuroscience, 2018, Volume 12
[8]
C. Klemann, L. Wagner, M. Stephan, and S. von Hörsten
Clinical & Experimental Immunology, 2016, Volume 185, Number 1, Page 1
[9]
L. Wagner, C. Klemann, M. Stephan, and S. von Hörsten
Clinical & Experimental Immunology, 2016, Volume 184, Number 3, Page 265
[11]
Leona Wagner, Florian Kaestner, Raik Wolf, Harald Stiller, Ulrich Heiser, Susanne Manhart, Torsten Hoffmann, Jens-Ulrich Rahfeld, Hans-Ulrich Demuth, Matthias Rothermundt, and Stephan von Hörsten
Neuropeptides, 2016, Volume 57, Page 21
[12]
Leona Wagner, Raik Wolf, Ulrike Zeitschel, Steffen Rossner, Åsa Petersén, Blair R. Leavitt, Florian Kästner, Matthias Rothermundt, Ulf-Torsten Gärtner, Daniel Gündel, Dagmar Schlenzig, Nadine Frerker, Jutta Schade, Susanne Manhart, Jens-Ulrich Rahfeld, Hans-Ulrich Demuth, and Stephan von Hörsten
Journal of Neurochemistry, 2015, Volume 135, Number 5, Page 1019
[13]
A.A. Spasov and N.I. Chepljaeva
Biomeditsinskaya Khimiya, 2015, Volume 61, Number 4, Page 488
[14]
Fabio Canneva, Yulia Golub, Joerg Distler, Julia Dobner, Sandra Meyer, and Stephan von Hörsten
Psychoneuroendocrinology, 2015, Volume 53, Page 195
[15]
A. A. Spasov and N. I. Chepljaeva
Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 2014, Volume 8, Number 4, Page 293
[16]
M. V. Robinson, E. V. Mel’nikova, and V. A. Trufakin
Bulletin of Experimental Biology and Medicine, 2014, Volume 158, Number 1, Page 66
[17]
Liehua Liu, Bilal Omar, Piero Marchetti, and Bo Ahrén
Biochemical and Biophysical Research Communications, 2014, Volume 453, Number 3, Page 398
[18]
Tihana Tasic, Michael Stephan, Stephan von Hörsten, Reinhard Pabst, and Andreas Schmiedl
Immunobiology, 2014, Volume 219, Number 11, Page 888
[19]
Yvonne K. Urbach, Kerstin A. Raber, Fabio Canneva, Anne-C. Plank, Theresa Andreasson, Henrik Ponten, Johan Kullingsjö, Huu Phuc Nguyen, Olaf Riess, and Stephan von Hörsten
Journal of Neuroscience Methods, 2014, Volume 234, Page 38
[20]
Katharina Luise Hupa, Andreas Schmiedl, Reinhard Pabst, Stephan Von Hörsten, and Michael Stephan
The Anatomical Record, 2014, Volume 297, Number 2, Page 317
[21]
Zhendi Wang, Christina Grigo, Julia Steinbeck, Stephan von Hörsten, Kerstin Amann, and Christoph Daniel
Peptides, 2014, Volume 57, Page 109
[22]
[23]
A. Schosser, D. Gaysina, S. Cohen-Woods, E. Domenici, J. Perry, F. Tozzi, A. Korszun, C. Gunasinghe, J. Gray, L. Jones, E.B. Binder, F. Holsboer, N. Craddock, M.J. Owen, I.W. Craig, A.E. Farmer, P. Muglia, and P. McGuffin
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2011, Volume 156, Number 6, Page 640
[24]
T. Tasic, W. Bäumer, A. Schmiedl, F. Schwichtenhövel, R. Pabst, U. Raap, S. von Hörsten, and M. Stephan
Clinical & Experimental Allergy, 2011, Volume 41, Number 8, Page 1098

Comments (0)

Please log in or register to comment.
Log in