The Role of Heparin Cofactor II in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice

• Material Type: 博士論文
• Title: The Role of Heparin Cofactor II in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice
• Author/Editor: Kurahashi, Kiyoe; Inoue, Seika; Yoshida, Sumiko; Ikeda, Yasumasa; Morimoto, Kana; Uemoto, Ryoko; Ishikawa, Kazue; Kondo, Takeshi; Yuasa, Tomoyuki; Endo, Itsuro; Miyake, Masato; Oyadomari, Seiichi; Matsumoto, Toshio; Abe, Masahiro; Sakaue, Hiroshi; Aihara, Ken-ichi
• Author Heading: Kurahashi, Kiyoe; Inoue, Seika; Yoshida, Sumiko; Ikeda, Yasumasa; Morimoto, Kana; Uemoto, Ryoko; Ishikawa, Kazue; Kondo, Takeshi; Yuasa, Tomoyuki; Endo, Itsuro; Miyake, Masato; Oyadomari, Seiichi; Matsumoto, Toshio; Abe, Masahiro; Sakaue, Hiroshi; Aihara, Ken-ichi
• Publication, Distribution, etc.: Japan Atherosclerosis Society
• Publication Date: 2017-12-01
• Publication Date (W3CDTF): 2017-12-01
• Alternative Title: ヒトおよびマウスのインスリン感受性と血糖恒常性維持におけるヘパリンコファクターIIの役割; Heparin Cofactor II and Hyperglycemia
• Periodical title: Journal of Atherosclerosis and Thrombosis
• No. or year of volume/issue: 24 12
• Volume: 24
• Issue: 12
• Pages: 1215-1230
• ISSN (Periodical Title): ISSN : 1880-3873; ISSN : 1340-3478
• Degree grantor/type: 徳島大学
• Date Granted: 2017-09-28
• Dissertation Number: 甲第3103号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: ヘパリンコファクターII; 糖尿病; インスリン抵抗性; 横断研究; ノックアウトマウス; Glucose homeostasis; Heparin cofactor II; High-fat diet; Humans; Mice
• Target Audience: 一般
• Note (General): Aim: Accelerated thrombin action is associated with insulin resistance. It is known that upon activation by binding to dermatan sulfate proteoglycans, heparin cofactor Ⅱ(HCⅡ) inactivates thrombin in tissues. Because HCⅡ may be involved in glucose metabolism, we investigated the relationship between plasma HCⅡ activity and insulin resistance. Methods and Results: In a clinical study, statistical analysis was performed to examine the relationships between plasma HCⅡ activity, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and homeostasis model assessment-insulin resistance (HOMA-IR) in elderly Japanese individuals with lifestyle-related diseases. Multiple regression analysis showed significant inverse relationships between plasma HCⅡ activity and HbA1c (p=0.014), FPG (p=0.007), and HOMA-IR (p= 0.041) in elderly Japanese subjects. In an animal study, HCⅡ＋/＋ mice and HCⅡ＋/− mice were fed with a normal diet or high-fat diet (HFD) until 25 weeks of age. HFD-fed HCⅡ＋/− mice exhibited larger adipocyte size, higher FPG level, hyperinsulinemia, compared to HFD-fed HCⅡ＋/＋ mice. In addition, HFD-fed HCⅡ＋/− mice exhibited augmented expression of monocyte chemoattractant protein-1 and tumor necrosis factor, and impaired phosphorylation of the serine/threonine kinase Akt and AMP-activated protein kinase in adipose tissue compared to HFD-fed HCⅡ＋/＋ mice. The expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase was also enhanced in the hepatic tissues of HFD-fed HCⅡ＋/− mice. Conclusions: The present studies provide evidence to support the idea that HCⅡ plays an important role in the maintenance of glucose homeostasis by regulating insulin sensitivity in both humans and mice. Stimulators of HCⅡ production may serve as novel therapeutic tools for the treatment of type 2 diabetes.
• Format (IMT): application/pdf
• Source: fulltext; https://repo.lib.tokushima-u.ac.jp/files/public/11/110925/20171129134811257130/k3103_abstract_review.pdf; https://repo.lib.tokushima-u.ac.jp/files/public/11/110925/20171129134811573751/k3103_fulltext.pdf
• Access Restrictions: インターネット公開
• Rights (production): Copyright©2017 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.
• Related Material (DOI): 10.5551/jat.37739
• Periodical Title (NCID): AA12022527; https://ci.nii.ac.jp/ncid/AA12022527
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ