Dipeptidyl peptidase-4 inhibitor, linagliptin, ameliorates endothelial dysfunction and atherogenesis in normoglycemic apolipoprotein-E deficient mice

• Material Type: 博士論文
• ISSN: 1537-1891
• Title: Dipeptidyl peptidase-4 inhibitor, linagliptin, ameliorates endothelial dysfunction and atherogenesis in normoglycemic apolipoprotein-E deficient mice
• Volume: 79
• Author/Editor: Salim, Hotimah Masdan; Fukuda, Daiju; Higashikuni, Yasutomi; Tanaka, Kimie; Hirata, Yoichiro; Yagi, Shusuke; Soeki, Takeshi; Shimabukuro, Michio; Sata, Masataka
• Author Heading: Salim, Hotimah Masdan; Fukuda, Daiju; Higashikuni, Yasutomi; Tanaka, Kimie; Hirata, Yoichiro; Yagi, Shusuke; Soeki, Takeshi; Shimabukuro, Michio; Sata, Masataka
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2015-08-13
• Publication Date (W3CDTF): 2015-08-13
• Alternative Title: DPP-4阻害薬のひとつリナグリプチンは，正常血糖アポリポ蛋白E欠損マウスにおける血管内皮機能を改善し，動脈硬化を抑制する
• Periodical title: Vascular Pharmacology
• Degree grantor/type: 徳島大学
• Date Granted: 2017-03-23
• Date Granted (W3CDTF): 2017-03-23
• Dissertation Number: 甲第3007号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3007号
• Text Language Code: eng
• Subject Heading: DPP-4 inhibitor; Endothelial function; GLP-1; Inflammation; Linagliptin; Oxidative stress
• Target Audience: 一般
• Note (General): Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have vasoprotective effects. This study investigated whether a recently approved DPP-4 inhibitor, linagliptin (Lina), suppresses atherogenesis in non-diabetic apolipoprotein-E deficient (ApoE−/−) mice, and examined its effects on endothelial function.Methods and results: Lina (10 mg/kg/day) was administered orally to ApoE−/− mice for 20 weeks. Lina reduced atherogenesis without alteration of metabolic parameters including blood glucose level compared with control (P b 0.05). Results of immunohistochemical analyses and quantitative RT-PCR demonstrated that Lina significantly decreased inflammatory molecule expression and macrophage infiltration in the atherosclerotic aorta. Lina administration to ApoE−/− mice for 9 weeks ameliorated endothelium-dependent vasodilation compared with that in untreated mice. Plasma active glucagon-like peptide-1 (GLP-1) level was significantly higher in the treated group (P b 0.05). Exendin-4 (Ex-4), a GLP-1 analog, ameliorated endothelium-dependent vasodilation impaired by palmitic acid (PA) in wild-type mouse aortic segments. Ex-4 promoted phosphorylation of eNOSSer1177 and Akt, both of which were abrogated by PA, in human umbilical vein endothelial cells. In addition, Lina administration to ApoE−/− mice decreased oxidative stress, as determined by urinary 8-OHdG secretion and NADPH oxidase subunit expression in the abdominal aorta.Conclusion: Lina inhibited atherogenesis in non-diabetic ApoE−/− mice. Amelioration of endothelial dysfunction associated with a reduction of oxidative stress by GLP-1 contributes to the atheroprotective effects of Lina.
• DOI: info:doi/10.1016/j.vph.2015.08.011; https://doi.org/info:doi/10.1016/j.vph.2015.08.011
• Persistent ID (NDL): info:ndljp/pid/10951842; https://dl.ndl.go.jp/pid/10951842
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2017-09-02T15:28:24+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/110139
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp