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

• 資料種別: 博士論文
• ISSN: 1880-3873
• タイトル: The Role of Heparin Cofactor II in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice
• 巻次・部編番号: 24 12
• 著者・編者: 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
• 著者標目: 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
• 出版事項: Japan Atherosclerosis Society
• 出版年月日等: 2017-12-01
• 出版年（W3CDTF）: 2017-12-01
• 並列タイトル等: 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
• タイトル（掲載誌）: Journal of Atherosclerosis and Thrombosis
• 授与機関名: 徳島大学
• 授与年月日: 2017-09-28
• 授与年月日（W3CDTF）: 2017-09-28
• 報告番号: 甲第3103号
• 学位: 博士（医学）
• 博論授与番号: 甲第3103号
• 本文の言語コード: eng
• 件名標目: 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
• 対象利用者: 一般
• 一般注記: 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.
• DOI: info:doi/10.5551/jat.37739; https://doi.org/info:doi/10.5551/jat.37739
• 国立国会図書館永続的識別子: info:ndljp/pid/11008886; https://dl.ndl.go.jp/pid/11008886
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 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
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2018-01-02T17:18:43+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: https://repo.lib.tokushima-u.ac.jp/110925
• 連携機関・データベース: 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