Project/Area Number |
09670711
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Nagoya University |
Principal Investigator |
OKUMURA Kenji Nagoya University, School of Medicine, Assistant Professor, 医学部, 講師 (40262901)
|
Co-Investigator(Kenkyū-buntansha) |
MATSUI Hideo School of Medicine, Medical Staff, 医学部, 医員
|
Project Period (FY) |
1997 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
Keywords | Hyperinsulinemia / Insulin resistance / LDL particle size / Apolipoprotein E / gene polymorphism / LDL particle size / Apolipoprotein E / Hb Aic / Insulin / triglyceride / 動脈硬化 |
Research Abstract |
1. Exogenous hyperinsulinemia in rats. The mechanism by which hyperinsulinemia promotes atherogenesis is unknown. The effects of hyperinsulinemia on risk factors for atherosclerosis were investigated by subcutaneously injecting rats daily with an insulin-zinc suspension for 12 weeks. Hyperinsulinemia indeed deposition of cholesterol esters and triglycerides, especially those containing monounsaturated fatty acids, and abnormal arachidonate distribution in LDL and tissues. Hyperinsulinemia induced by high-fructose feedings in rats Two-weeks feeding of 40% fructose and 7% lard diet resulted in insulin resistance accompanied with high blood pressure in rats. The fatty acid composition of skeletal-muscle triglycerides demonstrated a higher percentage of saturated and monounsaturated fatty acids and a lower percentage of polyunsaturated fatty acids. Bezafibrate, not probucol, virtually normalized the fatty acid composition and insulin resistance. 3. LDL particle size and insulin Since LDL particle size appears to be associated with ischemic coronary artery disease, we evaluated the influence of insulin on the variation in LDL particle size in 210 subjects. LDL size was positively correlated with HDL cholesterol, and was inversely correlated with cholesterol, TG, glucose, fasting insulin, Hb A 1c and body mass index. In response to a 75 g oral glucose load, LDL size was changed according to the pre-load size and insulin levels. One genetic factor to determine the LDL size was Apolipoprotein E- ε 4 allete. Angiotensin converting enzyme I/D genotype was not associated with LDL size.
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