β2-adrenoceptor polymorphisms relate to insulin resistance and sympathetic overactivity as early markers of metabolic disease in nonobese, normotensive individuals
β2-adrenoceptor polymorphisms relate to insulin resistance and sympathetic overactivity as early markers of metabolic disease in nonobese, normotensive individuals
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DOI：
10.1016/j.amjhyper.2005.01.006
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发表时间：
2005-07-01
影响因子：
3.2
通讯作者：
Tuck, ML
中科院分区：
文献类型：
--
作者：
Masuo, K;Katsuya, T;Tuck, ML
背景：负责胰岛素抵抗的基因也是胰岛素抵抗相关疾病的候选基因，例如肥胖和高血压。据报道，β（2）和β（3） - 肾上腺素受体的功能多态性与糖尿病，高血压和肥胖有关。为了澄清β-肾上腺素能受体多态性与胰岛素抵抗的相关性，我们研究了它们与β（2）（2）（Arg16gly，gln27glu）和beta（3）（3）（tfp64arg）adrenopector genes.methods.methods的相关性：日本男性使用胰岛素抵抗的体内平衡模型评估（HOMA-IR）将个体分为胰岛素敏感和耐胰岛素的群体。参与者中的胰岛素抵抗被定义为HOMA-IR等于或大于平均加上3.1的平均水平。有69名耐胰岛素的男性和86名对胰岛素敏感的男性。体重指数（BMI），血压（BP），血浆葡萄糖，胰岛素，瘦素，去甲肾上腺素（NE）水平以及beta（2）的Arg16gly和Gln27Glu的多态性（2） - 和beta（3）-Adrenrenoceptor的Trp64arg（3）在所有参与者中均测量了多态性。与胰岛素敏感的组相比，胰岛素耐药组的Gly16等位基因的频率更高，而GLN27GLU和TRP64ARG的基因型或等位基因的频率相似。与胰岛素敏感组的水平相比，胰岛素耐药组的HOMA-IR，禁食胰岛素，NE和总脂肪质量更高，但BMI和瘦素水平相似。携带Beta（2） - 肾上腺素受体基因的Gly16等位基因的受试者具有比没有Gly16等位基因的那些（bela conconele conconey：beta的Gly16突变）更高的平均honia-hor-honia-hor-honia-hiria-horia-ir，ne NE，体内脂肪质量和BP。 2） - 肾上腺肾上腺素基因与胰岛素抵抗，肥胖和BP的增加有关，并伴有较高的血浆NE水平。发展肥胖症的代谢疾病。这些发现表明，β2-肾上腺素基基因多态性在高血压和肥胖症中胰岛素抵抗的关联中的重要作用。
Background: The genes responsible for insulin resistance are also candidate genes for insulin resistance-related diseases, such as obesity and hypertension. Functional polymorphisms in the beta(2)- and beta(3)-adrenergic receptors have been reported to be associated with diabetes, hypertension, and obesity. To clarify the relevance of the beta-adrenergic receptor polymorphisms to insulin resistance, we studied their association with polymorphisms of beta(2) (Arg16Gly, Gln27Glu) and beta(3) (Tfp64Arg) adrenoceptor genes.Methods: We studied 155 young, nonobese Japanese men using the homeostasis model assessment of insulin resistance (HOMA-IR) to divide individuals into insulin-sensitive and insulin-resistant groups. Insulin resistance in the participants was defined as HOMA-IR equal to or greater than the average plus 1 SD of 3.1. There were 69 men who were insulin resistant and 86 men who were insulin sensitive. Body mass index (BMI), blood pressure (BP), plasma glucose, insulin, leptin, norepinephrine (NE) levels, and the polymorphisms of Arg16Gly and Gln27Glu of the beta(2)- and Trp64Arg of the beta(3)-adrenoceptor polymorphisms were measured in all participants.Results: The insulin-resistant group had higher frequency of the Gly16 allele of Arg16Gly compared with the insulin-sensitive group, whereas the frequencies of genotypes or alleles of Gln27Glu and Trp64Arg were similar. The insulin-resistant group had a higher mean HOMA-IR, fasting insulin, NE, and total fat mass compared with levels in the insulin-sensitive group, but the BMI and leptin levels were similar. The subjects carrying the Gly16 allele of the beta(2)-adrenoceptor gene had a higher mean HONIA-IR, fasting insulin, NE, body fat mass, and BP than those without the Gly16 allele.Conclusions: The Gly16 mutation of the beta(2)-adrenoceptor gene is associated with increased insulin resistance, adiposity, and BP accompanied by higher plasma NE levels early in the metabolic disease in developing obesity. These findings show an important role of beta 2-adrenoceptor gene polymorphisms in the association of insulin resistance in hypertension and obesity.