Bitter taste receptors influence glucose homeostasis.
Bitter taste receptors influence glucose homeostasis.
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DOI：
10.1371/journal.pone.0003974
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Munger SD
中科院分区：
文献类型：
--
作者：
Dotson CD;Zhang L;Xu H;Shin YK;Vigues S;Ott SH;Elson AE;Choi HJ;Shaw H;Egan JM;Mitchell BD;Li X;Steinle NI;Munger SD
TAS1R-和tas2r型味觉受体分别在味觉系统中表达，在那里它们分别检测甜味和苦味刺激。这些受体也在哺乳动物胃肠道的细胞亚群中表达，在那里它们介导营养同化和内分泌反应。例如，甜味剂刺激肠肠内分泌L细胞表面的味觉受体，引起细胞内Ca2+的增加和胰高血糖素样肽-1 （GLP-1）的分泌，胰高血糖素样肽-1是胰岛素生物合成和分泌的重要调节剂。由于味觉感受器在调节食物摄入和对化学刺激的消化反应中的重要性，我们假设味觉感受器功效的差异可能会影响葡萄糖稳态。为了解决这个问题，我们在阿米什家族糖尿病研究中启动了一项候选基因研究，并评估了味觉受体变异与葡萄糖失调指标的关系，包括2型糖尿病的诊断和口服葡萄糖耐量试验期间的高水平血糖和胰岛素。我们报道TAS2R单倍型与葡萄糖和胰岛素稳态改变有关。我们还发现，该单倍型中的一个SNP破坏了单个受体TAS2R9对其同源配体氧氟沙星、普鲁卡因酰胺和吡氮平的正常反应。总之，这些发现表明TAS2R受体功能受损会对葡萄糖稳态产生负面影响，在消化化学感觉和代谢疾病之间提供了重要的联系。
TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca2+ and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1), an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease.
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影响因子：
30.8
作者：
Bufe, B;Hofmann, T;Meyerhof, W
通讯作者：
Meyerhof, W
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
9.2
作者：
Bufe, B;Breslin, PAS;Meyerhof, W
通讯作者：
Meyerhof, W
影响因子：
64.5
作者：
Chandrashekar, J;Mueller, KL;Ryba, NJP
通讯作者：
Ryba, NJP
DOI：
10.1073/pnas.0706890104
发表时间：
2007-09-18
影响因子：
11.1
作者：
Jang, Hyeung-Jin;Kokrashvili, Zaza;Egan, Josephine M.
通讯作者：
Egan, Josephine M.