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ID 110925
タイトル別表記
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 
著者
倉橋, 清衛 徳島大学大学院医科学教育部(プロテオミクス医科学専攻) 徳島大学 教育研究者総覧
Inoue, Seika Tokushima University
森本, 佳奈 Tokushima University
Uemoto, Ryoko Tokushima University
Ishikawa, Kazue Tokushima University
キーワード
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
資料タイプ
学位論文
抄録
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.
掲載誌名
Journal of Atherosclerosis and Thrombosis
ISSN
18803873
13403478
cat書誌ID
AA12022527
出版者
Japan Atherosclerosis Society
24
12
開始ページ
1215
終了ページ
1230
発行日
2017-12-01
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Kiyoe Kurahashiの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
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.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3103号
学位記番号
甲医第1347号
学位授与年月日
2017-09-28
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系
先端酵素学研究所