The dipeptidyl peptidase-4 inhibitor linagliptin preserves endothelial function in mesenteric arteries from type 1 diabetic rats without decreasing plasma glucose

Salheen, S, Panchapakesan, U, Pollock, C and Woodman, O 2015, 'The dipeptidyl peptidase-4 inhibitor linagliptin preserves endothelial function in mesenteric arteries from type 1 diabetic rats without decreasing plasma glucose', PLoS ONE, vol. 10, no. 11, e0143941, pp. 1-15.


Document type: Journal Article
Collection: Journal Articles

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Title The dipeptidyl peptidase-4 inhibitor linagliptin preserves endothelial function in mesenteric arteries from type 1 diabetic rats without decreasing plasma glucose
Author(s) Salheen, S
Panchapakesan, U
Pollock, C
Woodman, O
Year 2015
Journal name PLoS ONE
Volume number 10
Issue number 11
Article Number e0143941
Start page 1
End page 15
Total pages 15
Publisher Public Library of Science
Abstract The aim of the study was to investigate the effect of the DPP-4 inhibitor linagliptin on the mechanism(s) of endothelium-dependent relaxation in mesenteric arteries from STZ-induced diabetic rats. Both normal and diabetic animals received linagliptin (2 mg/kg) daily by oral gavage for a period of 4 weeks. To measure superoxide generation in mesenteric arteries, lucigenin-enhanced chemiluminescence was used. ACh-induced relaxation of mesenteric arteries was assessed using organ bath techniques and Western blotting was used to investigate protein expression. Pharmacological tools (1μM TRAM-34, 1μM apamin, 100 nM Ibtx, 100 μM L-NNA, 10 μM ODQ) were used to distinguish between NO and EDH-mediated relaxation. Linagliptin did not affect plasma glucose, but did decrease vascular superoxide levels. Diabetes reduced responses to ACh but did not affect endothelium-independent responses to SNP. Linagliptin improved endothelial function indicated by a significant increase in responses to ACh. Diabetes impaired the contribution of both nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) to endothelium-dependent relaxation and linagliptin treatment significantly enhanced the contribution of both relaxing factors. Western blotting demonstrated that diabetes also increased expression of Nox2 and decreased expression and dimerization of endothelial NO synthase, effects that were reversed by linagliptin. These findings demonstrate treatment of type 1 diabetic rats with linagliptin significantly reduced vascular superoxide levels and preserved both NO and EDH-mediated relaxation indicating that linagliptin can improve endothelial function in diabetes independently of any glucose lowering activity.
Subject Pharmacology and Pharmaceutical Sciences not elsewhere classified
Keyword(s) Glucagon-like peptide-1
Dependent relaxation
Nitric-oxide
Blood-pressure
Growth-factor
Zdf rats
Dysfunction
Impairment
Mechanisms
Mellitus
DOI - identifier 10.1371/journal.pone.0143941
Copyright notice © 2015 Salheen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.
ISSN 1932-6203
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