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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1437-4315
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Volume 392, Issue 3

Issues

DPP-4 inhibition increases GIP and decreases GLP-1 incretin effects during intravenous glucose tolerance test in Wistar rats

Ernst-Joachim Freyse / Sabine Berg / Klaus-Dieter Kohnert / Peter Heinke / Eckhard Salzsieder
Published Online: 2011-06-18 | DOI: https://doi.org/10.1515/bc.2011.027

Abstract

GIP metabolite [GIP (3–42)] and GLP-1 metabolite [GLP-1 (9–36) amide] have been reported to differ with regard to biological actions. Systemic DPP-4 inhibition can therefore reveal different actions of GIP and GLP-1. In catheter wearing Wistar rats, insulinotropic effects of equipotent doses of GIP (2.0 nmol/kg) and GLP-1 (7–36) amide (4.0 nmol/kg) and vehicle were tested in the absence/presence of DPP-4 inhibition. Blood glucose and insulin were frequently sampled. DPP-4 inhibitor was given at -20 min, the incretin at -5 min and the intravenous glucose tolerance test (0.4 g glucose/kg) commenced at 0 min. G-AUC and I-AUC, insulinogenic index and glucose efflux, were calculated from glucose and insulin curves. Systemic DPP-4 inhibition potentiated the acute GIP incretin effects: I-AUC (115±34 vs. 153±39 ng·min/ml), increased the insulinogenic index (0.74±0.24 vs. 0.99±0.26 ng/mmol), and improved glucose efflux (19.8±3.1 vs. 20.5±5.0 min-1). The GLP-1 incretin effects were diminished: I-AUC (124±18 vs. 106±38 ng·min/ml), the insulinogenic index was decreased (0.70±0.18 vs. 0.50±0.19 ng/mmol), and glucose efflux declined (14.9±3.1 vs. 11.1±3.7 min-1). GLP-1 and GIP differ remarkably in their glucoregulatory actions in healthy rats when DPP-4 is inhibited. These previously unrecognized actions of DPP-4 inhibitors could have implications for future use in humans.

Keywords: dipeptidyl peptidase-4 inhibitor; GIP; GLP-1; incretin actions; intravenous glucose tolerance test (IVGTT); rat

About the article

Corresponding author


Received: 2010-07-05

Accepted: 2010-11-12

Published Online: 2011-06-18

Published in Print: 2011-03-01


Citation Information: Biological Chemistry, Volume 392, Issue 3, Pages 209–215, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/bc.2011.027.

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[1]
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[2]
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Biological Chemistry, 2011, Volume 392, Number 3

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