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ID 110925
Title Alternative
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 
Author
Inoue, Seika Tokushima University
Morimoto, Kana Tokushima University
Uemoto, Ryoko Tokushima University
Ishikawa, Kazue Tokushima University
Keywords
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
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Journal of Atherosclerosis and Thrombosis
ISSN
18803873
13403478
NCID
AA12022527
Publisher
Japan Atherosclerosis Society
Volume
24
Issue
12
Start Page
1215
End Page
1230
Published Date
2017-12-01
Remark
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。
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3103号
Diploma Number
甲医第1347号
Granted Date
2017-09-28
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences
Institute of Advanced Medical Sciences