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Inter-relationship between lipoprotein and glucose metabolism-analysis using stable isotope study

脂蛋白和葡萄糖代谢之间的相互关系——使用稳定同位素研究进行分析

基本信息

批准号：
17590949
负责人：
IKEWAKI Katsunori
金额：
$ 1.92万
依托单位：
JIKEI UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Metabolic syndrome is characterized by impaired lipid and glucose metabolism based upon central obesity and insulin resistance. In this sense, interrelationship between lipid and glucose metabolism has been expected. In order to elucidate this possible relationship, we employed triple tracer study in which stable isotopically labeled leucine, glycerol, and glucose are injected to investigate apoliporotein, VLDL glycerol, and glucose metabolism, respectively. Pitavastatin reduced VLDL apoB levels by 43%, which was due combined to 39% increase in catabolism and 23% reduction of production. As to IDL, IDL apoB levels were decreased by 44% which was primarily due to 44% increase in catabolism. LDL apoB was decreased by 33% and this was entirely due to the increased LDL apoB catabolism. VLDL TG reduction was due to increased catabolism as well as reduction of production. Pitavastatin had no significant influence on either insulin sensitivity or glucose sensitivity. Correlation analysis revealed that insulin sensitivity correlated positively with VLDL apoB metabolism. These observation therefore suggest that apoliporpoteins and glucose metabolism associated each other and potent statin such as pitavasitatin could be effective to favorably modify lipid abnormalities typically observed in patients with metabolic syndrome.

代谢综合征的特征是基于中心性肥胖和胰岛素抵抗的脂质和葡萄糖代谢受损。从这个意义上说，脂质和葡萄糖代谢之间的相互关系是可以预期的。为了阐明这种可能的关系，我们采用了三重示踪剂研究，其中注射稳定同位素标记的亮氨酸、甘油和葡萄糖，分别研究载脂蛋白、VLDL 甘油和葡萄糖代谢。匹伐他汀使 VLDL apoB 水平降低 43%，这是由于分解代谢增加 39%，产量减少 23%。至于 IDL，IDL apoB 水平下降了 44%，这主要是由于分解代谢增加了 44%。 LDL apoB 降低了 33%，这完全是由于 LDL apoB 分解代谢增加。 VLDL TG 减少是由于分解代谢增加以及产量减少。匹伐他汀对胰岛素敏感性或葡萄糖敏感性没有显着影响。相关分析显示胰岛素敏感性与VLDL apoB代谢呈正相关。因此，这些观察结果表明，载脂蛋白和葡萄糖代谢相互关联，并且有效的他汀类药物（例如匹伐他汀）可以有效地改善通常在代谢综合征患者中观察到的脂质异常。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients

DOI：
10.1038/sj.ki.5002131
发表时间：
2007-05-01
期刊：
KIDNEY INTERNATIONAL
影响因子：
19.6
作者：
Frischmann, M. E.;Kronenberg, F.;Dieplinger, H.
通讯作者：
Dieplinger, H.

Metabolism of ApoB lipoproteins of intestinal and hepatic origin during constant feeding of small amounts of fat.

持续喂食少量脂肪期间，肠道和肝脏来源的 ApoB 脂蛋白的代谢。

DOI：
发表时间：
2006
期刊：
J Lipid Res. 47
影响因子：
0
作者：
Shinohara T;Ueda A;Abe-Dohmae S.;Tsujita M.;Hayashi M.;Tsujita M. et al.;Hayashi M. et al.;Cuchel M;Frischmann ME;Mochizuki S;Cuchel M;Cuchel M;Frischmann ME;Mochizuki S;Nishiwaki M;Zheng C;Abe Y;Nishiwaki M;Zheng C
通讯作者：
Zheng C

Reduction in Cholesterol in Homozygous Familial Hypercholesterolemia with an Inhibitor of the Microsomal Triglyceride Transfer Protein.

使用微粒体甘油三酯转移蛋白抑制剂降低纯合子家族性高胆固醇血症中的胆固醇。

DOI：
发表时间：
2007
期刊：
New Engl. J. Med. 356
影响因子：
0
作者：
Oike;Y.;Akao;M.;Kubota;Y.;Suda;T.;Cuchel M
通讯作者：
Cuchel M

Human lecithin:cholesterol acyltransferase deficiency: in vivo kinetics of low-density lipoprotein and lipoprotein-X.

人卵磷脂：胆固醇酰基转移酶缺乏症：低密度脂蛋白和脂蛋白-X 的体内动力学。

DOI：
10.1161/01.atv.0000217910.90210.99
发表时间：
2006
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
0
作者：
Nishiwaki,Masato;Ikewaki,Katsunori;Bader,Giovanni;Nazih,Hassan;Hannuksela,Minna;Remaley,AlanT;Shamburek,RobertD;BrewerJr,HBryan
通讯作者：
BrewerJr,HBryan

Pravastatin prevents myocardium from ischemia-induced fibrosis by protecting vascular endothelial cells exposed to oxidative stress