Wagner Robert, Li Jia, Kenar Erhan, Kohlbacher Oliver, Machicao Fausto, Häring Hans-Ulrich, Fritsche Andreas, Xu Guowang, Lehmann Rainer
1] Division of Endocrinology, Diabetology, Angiology and Nephrology, Department of Internal Medicine 4, University Hospital Tuebingen, Germany [2] Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tuebingen, Tuebingen, Germany [3] German Center for Diabetes Research (DZD), Tübingen [4].
1] CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China [2].
Sci Rep. 2014 Jun 13;4:5296. doi: 10.1038/srep05296.
An important role of the type 2 diabetes risk variant rs7903146 in TCF7L2 in metabolic actions of various tissues, in particular of the liver, has recently been demonstrated by functional animal studies. Accordingly, the TT diabetes risk allele may lead to currently unknown alterations in human. Our study revealed no differences in the kinetics of glucose, insulin, C-peptide and non-esterified fatty acids during an OGTT in homozygous participants from a German diabetes risk cohort (n = 1832) carrying either the rs7903146 CC (n = 15) or the TT (n = 15) genotype. However, beta-cell function was impaired for TT carriers. Covering more than 4000 metabolite ions the plasma metabolome did not reveal any differences between genotypes. Our study argues against a relevant impact of TCF7L2 rs7903146 on the systemic level in humans, but confirms the role in the pathogenesis of type 2 diabetes in humans as a mechanism impairing insulin secretion.
近期，功能性动物研究证实了2型糖尿病风险变异体rs7903146在TCF7L2中对各种组织（尤其是肝脏）的代谢作用具有重要影响。因此，TT糖尿病风险等位基因可能会导致人类目前尚不清楚的改变。我们的研究发现，在一个德国糖尿病风险队列中，携带rs7903146 CC基因型（n = 15）或TT基因型（n = 15）的纯合参与者在口服葡萄糖耐量试验期间，葡萄糖、胰岛素、C肽和非酯化脂肪酸的动力学没有差异。然而，TT携带者的β细胞功能受损。覆盖4000多个代谢物离子的血浆代谢组未显示出基因型之间的任何差异。我们的研究表明，TCF7L2 rs7903146对人类全身水平没有相关影响，但证实了其作为损害胰岛素分泌的机制在人类2型糖尿病发病机制中的作用。
