Slc2a5 (Glut5) Is Essential for the Absorption of Fructose in the Intestine and Generation of Fructose-induced Hypertension
Slc2a5 (Glut5) Is Essential for the Absorption of Fructose in the Intestine and Generation of Fructose-induced Hypertension
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DOI：
10.1074/jbc.m808128200
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发表时间：
2009-02-20
影响因子：
4.8
通讯作者：
Soleimani, Manoocher
中科院分区：
文献类型：
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作者：
Barone, Sharon;Fussell, Stacey L.;Soleimani, Manoocher
体内肠道中负责果糖吸收的转运体的身份及其在果糖诱导的高血压中的潜在作用仍然是推测性的。本研究表明，与野生型小鼠相比，Glut5 （Slc2a5）缺失使空肠中的果糖吸收减少了75%，血清果糖浓度降低了90%。当给对照组（60%淀粉）喂食时，Glut5（-/-）小鼠血压正常，体重增加正常。然而，在高果糖（60%果糖）饮食喂养14周后，Glut5（-/-）小鼠空肠对盐的吸收增强，并出现全身性高血压，而Glut5（-/-）小鼠空肠没有表现出果糖刺激的盐吸收，而且在高果糖饮食开始后的3-5天，它们的肠道营养吸收出现了明显的障碍，并伴有低血压。对饲喂高果糖饮食的Glut5（-/-）小鼠的肠道检查显示，盲肠和结肠大量扩张，与严重的吸收不良相一致，并伴有独特的适应性离子转运蛋白上调。与果糖吸收不良相反，当喂食高葡萄糖（60%葡萄糖）饮食时，Glut5（-/-）小鼠没有表现出吸收缺陷。我们得出结论，Glut5对于肠道中果糖的吸收至关重要，并在果糖诱导的高血压的产生中起着重要作用。只有当动物被喂食高果糖饮食时，Glut5的缺失才会导致严重的营养吸收缺陷和体积减少，并与结肠中离子吸收转运蛋白的代偿性适应性上调有关。
The identity of the transporter responsible for fructose absorption in the intestine in vivo and its potential role in fructose-induced hypertension remain speculative. Here we demonstrate that Glut5 (Slc2a5) deletion reduced fructose absorption by similar to 75% in the jejunum and decreased the concentration of serum fructose by similar to 90% relative to wild-type mice on increased dietary fructose. When fed a control (60% starch) diet, Glut5(-/-) mice had normal blood pressure and displayed normal weight gain. However, whereas Glut5(-/-) mice showed enhanced salt absorption in their jejuna in response to luminal fructose and developed systemic hypertension when fed a high fructose (60% fructose) diet for 14 weeks, Glut5(-/-) mice did not display fructose-stimulated salt absorption in their jejuna, and they experienced a significant impairment of nutrient absorption in their intestine with accompanying hypotension as early as 3-5 days after the start of a high fructose diet. Examination of the intestinal tract of Glut5(-/-) mice fed a high fructose diet revealed massive dilatation of the caecum and colon, consistent with severe malabsorption, along with a unique adaptive up-regulation of ion transporters. In contrast to the malabsorption of fructose, Glut5(-/-) mice did not exhibit an absorption defect when fed a high glucose (60% glucose) diet. We conclude that Glut5 is essential for the absorption of fructose in the intestine and plays a fundamental role in the generation of fructose-induced hypertension. Deletion of Glut5 results in a serious nutrient-absorptive defect and volume depletion only when the animals are fed a high fructose diet and is associated with compensatory adaptive up-regulation of ion-absorbing transporters in the colon.