Lipid metabolism in hyperinsulinemia and insulin resistance and atheroscleorosis

高胰岛素血症、胰岛素抵抗和动脉粥样硬化中的脂质代谢

• 批准号: 09670711
• 负责人: OKUMURA Kenji
• 金额: $ 1.79万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670711/
• 关键词: Hyperinsulinemia; Insulin resistance; LDL particle size; Apolipoprotein E; gene polymorphism; LDL particle size; Apolipoprotein E; Hb Aic; Insulin; triglyceride; 動脈硬化

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 ratsTwo-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 insulinSince 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.

1.大鼠外源性高胰岛素血症：高胰岛素血症促进动脉粥样硬化形成的机制尚不清楚。高胰岛素血症对动脉粥样硬化危险因素的影响进行了研究，每天皮下注射胰岛素锌混悬液，持续12周。高胰岛素血症主要表现为胆固醇酯和甘油三酯的沉积，尤其是单不饱和脂肪酸的沉积，以及花生四烯酸在LDL和组织中的异常分布。高果糖喂养大鼠引起高胰岛素血症。肌肉甘油三酯的脂肪酸组成表现出较高的饱和和单不饱和脂肪酸的百分比和较低的多不饱和脂肪酸的百分比。苯扎贝特，而不是普罗布考，实际上使脂肪酸组成和胰岛素抵抗正常化。LDL颗粒大小和胰岛素由于LDL颗粒大小似乎与缺血性冠状动脉疾病有关，我们在210名受试者中评估了胰岛素对LDL颗粒大小变化的影响。LDL大小与HDL胆固醇呈正相关，与胆固醇、TG、血糖、空腹胰岛素、HbA 1c和体重指数呈负相关。响应于75 g口服葡萄糖负荷，LDL大小根据预负荷大小和胰岛素水平而改变。决定LDL大小的一个遗传因素是载脂蛋白E- ε 4等位基因。血管紧张素转换酶I/D基因型与LDL大小无关。

项目成果

Matsui, H. et al.: "Improved insulin sensitivity by bezafibrate in rats"Diabetes. 46. 348-353 (1996)

Matsui, H. 等人：“通过苯扎贝特改善大鼠的胰岛素敏感性”糖尿病。

Okumura K, Matsui H, Kawakami K, Numaguchi Y, Hayakawa M, Morishima I, Toki Y, Ito T.: "Low density lipoprotein particle size is associated with glycosylated hemoglobin levels regardless of plasma lopid levels"Intern Med. 37. 273-279 (1998)

Okumura K、Matsui H、Kawakami K、Numaguchi Y、Hayakawa M、Morishima I、Toki Y、Ito T.：“低密度脂蛋白颗粒大小与糖基化血红蛋白水平相关，无论血浆脂质水平如何”Intern Med。

Okumura K, Matsui H, Kawakami K, Morishima I, Numaguchi Y, Murase K, Toki Y, Ito T.: "Modulation of LDL particle size after an oral glucose load is associated with insulin levels"Clin Chem Acta. 276. 143-155

Okumura K、Matsui H、Kawakami K、Morishima I、Numaguchi Y、Murase K、Toki Y、Ito T.：“口服葡萄糖负荷后 LDL 粒径的调节与胰岛素水平相关”Clin Chem Acta。

Okumura K, Matsui H, Kawakami K, Numaguchi Y, Kaneko S, Morishima I, Mokuno S, Toki Y, Hayakawa T.: "Relationship between the apolopoprotein E and angiotensin-covering enzyme genotypes and LDL particle size in Japanese subjects"Clin Chem Acta. 285. 91-103

Okumura K、Matsui H、Kawakami K、Numaguchi Y、Kaneko S、Morishima I、Mokuno S、Toki Y、Hayakawa T.：“日本受试者中载脂蛋白 E 与血管紧张素覆盖酶基因型和 LDL 粒径之间的关系”Clin Chem

K.Okumura,et al.: "Relationship between the apolipoprotein E and angiotensin-converting enzyme genotypes and LDL particle size in Japanese subjects."Clinic Chimica Acta. 285. 91-103 (1999)

K.Okumura 等人：“日本受试者中载脂蛋白 E 和血管紧张素转换酶基因型以及 LDL 粒径之间的关系。”Clinic Chimica Acta。