Decreased expression of glucose and peptide transporters in rat remnant kidney.
Decreased expression of glucose and peptide transporters in rat remnant kidney.
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DOI：
10.2133/dmpk.19.41
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发表时间：
2004-02-01
影响因子：
2.1
通讯作者：
Inui, Ken-ichi
中科院分区：
文献类型：
--
作者：
Nakamura, Nobuhiko;Masuda, Satohiro;Inui, Ken-ichi
肾脏质量的丧失会导致肾小管肥大和肾小球硬化，最终导致肾脏疾病的终末期。然而，关于慢性肾功能衰竭条件下肾小管葡萄糖的适应性和肽重吸收的信息很少。在本研究中，我们对16周的5/6肾切除大鼠的肾小管重吸收过滤的葡萄糖和小肽进行了功能和分子分析，作为慢性肾功能衰竭的模型。在5/6肾切除或假手术后16周，取肾皮质刷状缘膜和总RNA，以评价Na(+)梯度依赖的D-葡萄糖和H(+)梯度依赖的甘氨酰肌氨酸的摄取。用竞争性聚合酶链式反应检测SGLT和PEPT的mRNA水平。肾切除大鼠尿葡萄糖/肌酐比值明显高于假手术对照组。与假手术对照组相比，肾切除大鼠肾刷状缘膜囊泡对Na(+)依赖的葡萄糖摄取显著减少。然而，刷状缘膜中的另一种次级活性转运系统--H(+)依赖的多肽转运系统仍保持不变。此外，动力学分析表明，SGLT1(高亲和力类型)和SGLT2(低亲和力类型)介导的Na(+)/葡萄糖摄取均显著降低Vmax，但Km值不明显。竞争性聚合酶链式反应显示SGLT2、PEPT1和PEPT2的mRNA表达水平显著降低，而SGLT1的表达水平无明显变化。这些发现表明，在慢性肾功能衰竭期间，SGLT2的丢失意味着肾性葡萄糖尿的高风险。
The loss of renal mass induces tubular hypertrophy as well as glomerular sclerosis and results in the end stage of renal disease. However, there is little information about adaptation of tubular glucose and peptide reabsorption under conditions of chronic renal failure. In the present study, we performed functional and molecular analyses focused on the tubular reabsorption of filtered glucose and small peptides using 5/6 nephrectomized rats at 16 weeks, as a model of chronic renal failure. Sixteen weeks after 5/6 nephrectomy or sham treatment, the brush-border membranes and total RNA were obtained from the renal cortex to evaluate the uptake of Na(+) gradient-dependent D-glucose and H(+) gradient-dependent glycylsarcosine. The amounts of SGLT and PEPT mRNA levels were quantified by competitive PCR. The urinary glucose/creatinine ratio was markedly higher in nephrectomized rats than in sham-operated controls. Na(+)-dependent glucose uptake by the isolated renal brush-border membrane vesicles was markedly decreased in nephrectomized rats compared with that in sham-operated controls. However, H(+)-dependent peptide transport, another secondary active transport system in the brush-border membranes, was maintained. In addition, kinetic analysis revealed that both SGLT1 (high-affinity type)- and SGLT2 (low-affinity type)-mediated Na(+)/glucose uptake had markedly decreased Vmax values, but not Km values. Furthermore, competitive PCR demonstrated that the mRNA expression levels of SGLT2, PEPT1 and PEPT2, but not SGLT1, were markedly depressed. These findings suggested that loss of SGLT2 during chronic renal failure implies a high risk of renal glucosuria.