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核磁共振测定代谢综合征和2型糖尿病非人类灵长类动物的脂蛋白异常情况。

Nuclear magnetic resonance-determined lipoprotein abnormalities in nonhuman primates with the metabolic syndrome and type 2 diabetes mellitus.

作者信息

Ding Shi-Ying, Tigno Xenia T, Hansen Barbara C

机构信息

Department of Physiology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.

出版信息

Metabolism. 2007 Jun;56(6):838-46. doi: 10.1016/j.metabol.2007.01.015.

Abstract

The lipid profile in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) is commonly characterized by increased levels of triglycerides and decreased levels of high-density lipoprotein (HDL) cholesterol. However, within each lipoprotein class, the changes are more complex. The present study defined the characteristics of dyslipidemia among nonhuman primates, using nuclear magnetic resonance (NMR) spectroscopy as well as the classic beta-quantification method, and examined the pattern of multiple lipoprotein fractions in relation to the main factors identified with the MetS. Seventy-three rhesus monkeys were classified into 3 groups: healthy monkeys, monkeys with MetS, and monkeys with T2DM. Characteristics of dyslipidemia in the MetS and T2DM groups included increased levels of triglyceride-rich very low-density lipoprotein, intermediate-density lipoprotein, and small, dense, low-density lipoprotein (LDL) particles. Reduced concentrations of large LDL and large HDL particles together with reduction of LDL and HDL particle sizes were also observed. Correlation analysis revealed that poor glycemic and lipid profiles, glucose intolerance, and insulin resistance were associated with an atherogenic NMR profile. Compared with the conventional lipid panel, the NMR lipoprotein profile presented in greater detail distinctive differences between the dyslipidemia of the MetS and that of diabetes and demonstrated significant and divergent shifts in both particle size and number within lipoprotein classes between those 2 groups. Detailed lipoprotein profiling may provide additional indicators for more timely intervention. Rhesus monkeys are likely to provide an excellent model for novel drug testing designed to address the specific differences in lipoprotein fraction profile across these 3 groups that reflect the progression of pathophysiology from normal to overt diabetes.

摘要

代谢综合征(MetS)和2型糖尿病(T2DM)患者的血脂谱通常表现为甘油三酯水平升高和高密度脂蛋白(HDL)胆固醇水平降低。然而,在每个脂蛋白类别中,变化更为复杂。本研究利用核磁共振(NMR)光谱以及经典的β定量方法定义了非人类灵长类动物血脂异常的特征,并研究了多种脂蛋白组分与MetS相关主要因素的关系模式。73只恒河猴被分为3组:健康猴、患有MetS的猴和患有T2DM的猴。MetS组和T2DM组血脂异常的特征包括富含甘油三酯的极低密度脂蛋白、中间密度脂蛋白以及小而密的低密度脂蛋白(LDL)颗粒水平升高。还观察到大LDL和大HDL颗粒浓度降低以及LDL和HDL颗粒大小减小。相关性分析显示,血糖和血脂谱不佳、葡萄糖耐量异常和胰岛素抵抗与致动脉粥样硬化的NMR谱相关。与传统血脂检测指标相比,NMR脂蛋白谱更详细地呈现了MetS血脂异常与糖尿病血脂异常之间的显著差异,并显示出这两组在脂蛋白类别内颗粒大小和数量上的显著且不同的变化。详细的脂蛋白谱分析可能为更及时的干预提供额外指标。恒河猴可能为新型药物测试提供一个优秀的模型,该测试旨在解决这三组脂蛋白组分谱的特定差异,这些差异反映了从正常到显性糖尿病的病理生理进展。

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