Mate Alfonso, Barfull Anna, Hermosa Angeles M, Gómez-Amores Lucía, Vázquez Carmen M, Planas Joana M
Department of Physiology and Zoology, University of Seville, Spain.
Am J Physiol Regul Integr Comp Physiol. 2006 Sep;291(3):R760-7. doi: 10.1152/ajpregu.00524.2005. Epub 2006 May 11.
Experimental models of hypertension, such as spontaneously hypertensive rats (SHR), show alterations in cellular sodium transport that affects Na(+)-coupled cotransport processes and has been involved in the pathogenesis of this disease. The objective of the present study was to analyze the kinetic properties of the sodium-dependent glucose transport in the jejunum and ileum of SHR and its genetic control, Wistar-Kyoto (WKY) rats, as well as the regulation of the transporter, SGLT1. In hypertensive rats, the increased systolic blood pressure was accompanied by an enhancement of serum aldosterone levels compared with WKY rats, but no alterations were found in their body weight or serum glucose/insulin levels. The values for d-glucose maximal rate of transport (V(max)) were 42 and 60% lower, respectively, in the jejunum and ileum of SHR than those from WKY rats. On the other hand, the values for the Michaelis constant (K(m)) were similar in both animal groups, as was the diffusive component of transport (K(d)). Immunoblotting and Northern blot analysis revealed the existence of a lower abundance of SGLT1 protein and mRNA in SHR. Moreover, hypertensive rats showed a decrease in the molecular mass of SGLT1 that could not be explained in terms of different glycosylation and/or phosphorylation levels or an alternative splicing in the expression of the protein. These findings demonstrate that SGLT1 is regulated at a transcriptional level in the intestine of hypertensive rats, and suggest that this transporter might participate in the dysregulation of sodium transport observed in hypertension.
高血压实验模型，如自发性高血压大鼠（SHR），显示出细胞钠转运的改变，这种改变影响钠偶联共转运过程，并参与了该疾病的发病机制。本研究的目的是分析SHR及其基因对照品Wistar-Kyoto（WKY）大鼠空肠和回肠中钠依赖性葡萄糖转运的动力学特性，以及转运体SGLT1的调节。与WKY大鼠相比，高血压大鼠收缩压升高伴随着血清醛固酮水平的升高，但体重或血清葡萄糖/胰岛素水平未发现改变。SHR空肠和回肠中d-葡萄糖最大转运速率（V(max)）的值分别比WKY大鼠低42%和60%。另一方面，两个动物组的米氏常数（K(m)）值相似，转运的扩散成分（K(d)）也是如此。免疫印迹和Northern印迹分析显示，SHR中SGLT1蛋白和mRNA的丰度较低。此外，高血压大鼠中SGLT1的分子量降低，这不能用不同的糖基化和/或磷酸化水平或蛋白质表达中的可变剪接来解释。这些发现表明，SGLT1在高血压大鼠肠道中受转录水平调控，并提示该转运体可能参与了高血压中观察到的钠转运失调。
