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首页> 美国卫生研究院文献>PLoS Clinical Trials >Glucose-Raising Polymorphisms in the Human Clock Gene Cryptochrome 2 (CRY2) Affect Hepatic Lipid Content
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Glucose-Raising Polymorphisms in the Human Clock Gene Cryptochrome 2 (CRY2) Affect Hepatic Lipid Content

机译：人类时钟基因Cryptochrome 2（CRY2）中的葡萄糖升高多态性影响肝脂质含量。

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Circadian rhythms govern vital functions. Their disruption provokes metabolic imbalance favouring obesity and type-2 diabetes. The aim of the study was to assess the role of clock genes in human prediabetes. To this end, genotype-phenotype associations of 121 common single nucleotide polymorphisms (SNPs) tagging ARNTL, ARNTL2, CLOCK, CRY1, CRY2, PER1, PER2, PER3, and TIMELESS were assessed in a study population of 1,715 non-diabetic individuals metabolically phenotyped by 5-point oral glucose tolerance tests. In subgroups, hyperinsulinaemic-euglycaemic clamps, intravenous glucose tolerance tests, and magnetic resonance imaging/spectroscopy were performed. None of the tested SNPs was associated with body fat content, insulin sensitivity, or insulin secretion. Four CRY2 SNPs were associated with fasting glycaemia, as reported earlier. Importantly, carriers of these SNPs’ minor alleles revealed elevated fasting glycaemia and, concomitantly, reduced liver fat content. In human liver tissue samples, CRY2 mRNA expression was directly associated with hepatic triglyceride content. Our data may point to CRY2 as a novel switch in hepatic fuel metabolism promoting triglyceride storage and, concomitantly, limiting glucose production. The anti-steatotic effects of the glucose-raising CRY2 alleles may explain why these alleles do not increase type-2 diabetes risk.
机译：昼夜节律控制重要功能。它们的破坏引起代谢失衡，有利于肥胖和2型糖尿病。该研究的目的是评估时钟基因在人类糖尿病前期中的作用。为此，在研究的1,715名非代谢性糖尿病个体中，评估了121种标记ARNTL，ARNTL2，CLOCK，CRY1，CRY2，PER1，PER2，PER3和TIMELESS的常见单核苷酸多态性（SNP）的基因型-表型关联。通过5点口服葡萄糖耐量试验。在亚组中，进行了高胰岛素血症，正常血糖钳夹，静脉内葡萄糖耐量试验和磁共振成像/光谱学检查。所测试的SNP均与体脂含量，胰岛素敏感性或胰岛素分泌无关。如前所述，四种CRY2 SNP与空腹血糖有关。重要的是，这些SNP的次要等位基因携带者显示出空腹血糖升高，并随之降低了肝脏脂肪含量。在人类肝脏组织样品中，CRY2 mRNA表达与肝甘油三酯含量直接相关。我们的数据可能表明CRY2是肝燃料代谢中的新开关，可促进甘油三酸酯的储存并因此限制了葡萄糖的产生。葡萄糖升高的CRY2等位基因的抗脂肪变性作用可以解释为什么这些等位基因不会增加2型糖尿病的风险。

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