| Effects of PKF275-055, a dipeptidyl peptidase-4 inhibitor, on the development of atherosclerotic lesions in apolipoprotein E-null mice. | |
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MedLine Citation:
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PMID: 22225957 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We recently discovered that glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide can both prevent the development of atherosclerosis in apolipoprotein E-null (Apoe(-/-)) mice. In the present study, we attempted to extend these findings to orally administered dipeptidyl peptidase (DPP)-4 inhibitor. Seventeen-week-old Apoe(-/-) mice fed an atherogenic diet were administered a DPP-4 inhibitor, vildagliptin analogue (PKF275-055 [PKF], 100 µm/[kg d]), in drinking water over a period of 4 weeks. Aortic atherosclerosis and oxidized low-density lipoprotein-induced foam cell formation were determined. Orally administered PKF increased plasma levels of active glucagon-like peptide-1 by 3.5-fold, increased total glucose-dependent insulinotropic polypeptide levels by 2-fold, reduced body weight by 13%, and reduced plasma cholesterol levels by 30%. Compared with drinking water controls, PKF significantly suppressed total aortic atherosclerotic lesions, atheromatous plaque in the aortic root, and macrophage accumulation in the aortic wall by 30% to 40% (P < .001). None of these changes were associated with the PKF-induced reductions in body weight and plasma cholesterol levels. Foam cell formation was suppressed by 40% in the exudate peritoneal macrophages obtained from the PKF-treated mice. The DPP-4 inhibitor prevents the development of atherosclerotic lesions by suppressing macrophage foam cell formation. |
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Authors:
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Michishige Terasaki; Masaharu Nagashima; Takuya Watanabe; Kyoko Nohtomi; Yusaku Mori; Akira Miyazaki; Tsutomu Hirano |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-5 |
Journal Detail:
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Title: Metabolism: clinical and experimental Volume: - ISSN: 1532-8600 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375267 Medline TA: Metabolism Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine, Tokyo 142-8666, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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