Dotimas James R, Lee Austin W, Schmider Angela B, Carroll Shannon H, Shah Anu, Bilen Julide, Elliott Kayla R, Myers Ronald B, Soberman Roy J, Yoshioka Jun, Lee Richard T
Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, United States.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, United States.
Elife. 2016 Oct 11;5:e18313. doi: 10.7554/eLife.18313.
Metabolic studies suggest that the absorptive capacity of the small intestine for fructose is limited, though the molecular mechanisms controlling this process remain unknown. Here we demonstrate that thioredoxin-interacting protein (Txnip), which regulates glucose homeostasis in mammals, binds to fructose transporters and promotes fructose absorption by the small intestine. Deletion of in mice reduced fructose transport into the peripheral bloodstream and liver, as well as the severity of adverse metabolic outcomes resulting from long-term fructose consumption. We also demonstrate that fructose consumption induces expression of Txnip in the small intestine. Diabetic mice had increased expression of Txnip in the small intestine as well as enhanced fructose uptake and transport into the hepatic portal circulation. The deletion of in mice abolished the diabetes-induced increase in fructose absorption. Our results indicate that Txnip is a critical regulator of fructose metabolism and suggest that a diabetic state can promote fructose uptake.
代谢研究表明，尽管控制这一过程的分子机制尚不清楚，但小肠对果糖的吸收能力是有限的。在这里，我们证明了硫氧还蛋白相互作用蛋白（Txnip），它在哺乳动物中调节葡萄糖稳态，与果糖转运体结合并促进小肠对果糖的吸收。小鼠中Txnip的缺失减少了果糖向外周血流和肝脏的转运，以及长期食用果糖导致的不良代谢结果的严重程度。我们还证明，食用果糖会诱导小肠中Txnip的表达。糖尿病小鼠小肠中Txnip的表达增加，同时果糖摄取以及向肝门静脉循环的转运增强。小鼠中Txnip的缺失消除了糖尿病诱导的果糖吸收增加。我们的结果表明，Txnip是果糖代谢的关键调节因子，并表明糖尿病状态可促进果糖摄取。
