Lack of association of apoE ε4 allele with insulin resistance

Lack of association of apoE ε4 allele with insulin resistance
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DOI:
10.1007/s00592-011-0255-3
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发表时间:
2012-02-01
期刊:
影响因子:
3.8
通讯作者:
Perseghin, Gianluca
Perseghin, Gianluca
中科院分区:
医学3区
文献类型:
--
作者:
Ragogna, Francesca;Lattuada, Guido;Perseghin, Gianluca

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ApoE是一种参与血浆脂蛋白代谢的多态性蛋白质;已证明ApoE 4等位基因以年龄依赖性方式与冠状动脉和主动脉粥样硬化相关,其介导机制未知。这项研究的目的是评估人类apoE亚型是否与正常葡萄糖耐量以及心血管疾病的代谢和炎症危险因素相关。对365名个体进行了ApoE基因型分析。其中,309人在吸收后条件下进行了研究,其中142人还接受了3小时OGTT;另外56名受试者通过胰岛素钳夹结合[6,6 - 2 H2]葡萄糖输注进行了研究。ApoE基因型频率与以前报道的相似,不受年龄和BMI的影响。空腹血糖、胰岛素、FFA、血脂、替代标志物(HOMA-IR、OGTT衍生指数)以及钳夹衍生参数或胰岛素敏感性和胰岛素分泌在apoE基因型之间无差异。血清脂肪因子浓度(瘦素,脂联素,β-内酰胺酶)和炎症标志物(血清空腹hsCRP和MCP 1/CCL 2)也没有不同的apoE基因型。在接受钳夹手术的年轻的β 4携带者亚组中,检测到更高的空腹内源性葡萄糖产生。ApoE基因型与胰岛素抵抗或胰岛素分泌改变无关,未检测到胰岛素抵抗综合征的典型循环内分泌、代谢和炎症特征异常。
ApoE is a polymorphic protein involved in the metabolism of plasma lipoproteins; the epsilon 4 allele was shown to be associated with coronary and aortic atherosclerosis in age-dependent fashion mediated by unknown mechanisms. This study was undertaken to assess whether the apoE isoforms in humans were associated with normal glucose tolerance and with metabolic and inflammatory risk factors of CVD. ApoE genotype was assessed in 365 individuals. Of those, 309 were studied in the postabsorptive conditions and 142 of them also underwent a 3h-OGTT; 56 additional subjects were studied by means of the insulin clamp in combination with [6,6-2H2] glucose infusion. ApoE genotype frequencies were similar to those previously reported and were not influenced by age and BMI. Fasting plasma glucose, insulin, FFA, the lipid profile, surrogate markers (HOMA-IR, OGTT-derived index) as well as the clamp-derived parameters or insulin sensitivity and insulin secretion were not different by apoE genotypes. Serum adipokines concentrations (leptin, adiponectin, resistin) and markers of inflammation (serum fasting hsCRP and MCP1/CCL2) were also not different by apoE genotypes. In the subgroup of young epsilon 4 carriers which underwent the clamp procedure, a higher fasting endogenous glucose production was detected. ApoE genotype was not associated with insulin resistance or altered insulin secretion, and no abnormalities in the typical circulating endocrine, metabolic, and inflammatory features of the insulin resistance syndrome were detected.