Becker B N, Kondo S, Cheng H F, Harris R C
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Kidney Int. 1997 Jul;52(1):87-92. doi: 10.1038/ki.1997.307.
Ambient glucose concentrations alter type 1 angiotensin II receptor (AT1R) expression in renal tissues. The direction of change in AT1R density may depend on the specific cell type and the capacity for that cell type to use glucose as an energy substrate. Given the effects of angiotensin II (Ang II) in proximal tubule epithelia, glucose-mediated fluctuations in AT1R expression could significantly alter tubular Na(+)-H+ exchange and volume reabsorption. To determine if glucose influenced AT1R expression in cultured proximal tubule epithelial cells, SV40-immortalized rabbit proximal tubule epithelial cells (RPTEC) were exposed to 25 mmol (hi-glc) or 5 mmol glucose-containing serum-free medium (lo-glc) for seven to nine days, with or without an alternative energy substrate, pyruvate. AT1R expression, assessed by quantitative reverse-transcription polymerase chain reaction and specific 125I-Ang II binding, decreased in lo-glc medium (% reduction AT1R mRNA expression: 52 +/- 8%; N = 6; P < 0.005 vs. hi-glc; % reduction specific 125I-Ang II binding: 48 +/- 12%; N = 12; P < 0.03 vs. hi-glc). AT1R mRNA expression and specific 125I-Ang II binding recovered to hi-glc levels following the addition of pyruvate [60 mmol] to lo-glc cells. To ascertain if a growth factor that increases glucose uptake in vivo also altered AT1R expression, RPTEC were cultured in hi-glc medium with or without exogenous insulin [100 nM]. Insulin addition increased AT1R mRNA expression and specific 125I-Ang II binding in a concentration-dependent manner. However, insulin (100 nM) addition to lo-glc cells did not significantly increase specific 125I-Ang II binding. These results suggest that AT1R expression in SV40-immortalized rabbit proximal tubule cells is significantly affected by the availability of energy substrate. Ultimately, changes in proximal tubule AT1R expression, mediated by elevated glucose concentrations and insulin, could contribute to sodium-dependent hypertension in the setting of hyperinsulinemia and hyperglycemia.
环境葡萄糖浓度会改变肾组织中1型血管紧张素II受体（AT1R）的表达。AT1R密度的变化方向可能取决于特定的细胞类型以及该细胞类型利用葡萄糖作为能量底物的能力。鉴于血管紧张素II（Ang II）对近端肾小管上皮细胞的作用，葡萄糖介导的AT1R表达波动可能会显著改变肾小管钠氢交换和容量重吸收。为了确定葡萄糖是否影响培养的近端肾小管上皮细胞中AT1R的表达，将SV40永生化兔近端肾小管上皮细胞（RPTEC）暴露于含25 mmol（高糖）或5 mmol葡萄糖的无血清培养基（低糖）中7至9天，同时添加或不添加替代能量底物丙酮酸。通过定量逆转录聚合酶链反应和特异性125I-Ang II结合评估的AT1R表达，在低糖培养基中降低（AT1R mRNA表达降低百分比：52±8%；N = 6；与高糖相比，P < 0.005；特异性125I-Ang II结合降低百分比：48±12%；N = 12；与高糖相比，P < 0.03）。在低糖细胞中添加丙酮酸[60 mmol]后，AT1R mRNA表达和特异性125I-Ang II结合恢复到高糖水平。为了确定一种在体内增加葡萄糖摄取的生长因子是否也会改变AT1R表达，将RPTEC在含或不含外源性胰岛素[100 nM]的高糖培养基中培养。添加胰岛素以浓度依赖的方式增加了AT1R mRNA表达和特异性125I-Ang II结合。然而，向低糖细胞中添加胰岛素（100 nM）并未显著增加特异性125I-Ang II结合。这些结果表明，SV40永生化兔近端肾小管细胞中AT1R的表达受能量底物可用性的显著影响。最终，由葡萄糖浓度升高和胰岛素介导的近端肾小管AT1R表达变化可能导致高胰岛素血症和高血糖情况下的钠依赖性高血压。
