Glucose dilates renal afferent arterioles via glucose transporter-1.
Glucose dilates renal afferent arterioles via glucose transporter-1.
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DOI：
10.1152/ajprenal.00409.2017
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发表时间：
2018-07
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影响因子：
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通讯作者：
Jie Zhang;Shan Jiang;Jin Wei;K. Yip;Lei Wang;E. Lai;Ruisheng Liu
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作者：
Jie Zhang;Shan Jiang;Jin Wei;K. Yip;Lei Wang;E. Lai;Ruisheng Liu
肾小球过度滤过发生在糖尿病的早期阶段。急性葡萄糖输注会增加肾小球滤过率。有人提出肾小球反馈反应的参与和葡萄糖对传入小动脉（Af-Arts）的直接影响。然而，触发 Af-Art 扩张的信号通路尚未完全确定。因此，在本研究中，我们使用离体小鼠 Af-Arts 进行灌注，测试了我们的假设，即葡萄糖浓度的增加会增强内皮一氧化氮合成活性，并通过葡萄糖转运蛋白 1 (GLUT1) 扩张 Af-Arts。我们从非糖尿病 C57BL/6 小鼠中分离并微灌注 Af-Arts。 Af-Arts 用去甲肾上腺素 (1 µM) 进行预收缩。当我们将灌注液中的 d-葡萄糖浓度从低 (5 mM) 切换到高 (30 mM) 时，预收缩的 Af-Arts 显着扩张 37.8 ± 7.1%，但 L-葡萄糖不会引发扩张。通过 RT-PCR 测量，在微分散 Af-Arts 中鉴定出 GLUT1 mRNA。当环境葡萄糖浓度增加时，还使用荧光探针测量了 Af-Art 中一氧化氮 (NO) 产生的变化。当 d-葡萄糖浓度从 5 mM 切换至 30 mM 时，Af-Art 中 NO 的生成显着增加 19.2 ± 6.2%（84.7 ± 4.1 至 101.0 ± 9.3 U/min）。 L-葡萄糖对 NO 的产生没有影响。 GLUT1选择性拮抗剂4-[({[4-(1,1-二甲基乙基)苯基]磺酰基}氨基)甲基]-N-3-吡啶基苯甲酰胺和一氧化氮合酶抑制剂NG-硝基-l-精氨酸甲酯阻断高葡萄糖诱导的NO生成和血管舒张。总之，我们证明葡萄糖浓度的增加通过刺激 GLUT1 介导的内皮源性 NO 的产生来扩张 Af-Art。
Glomerular hyperfiltration occurs during the early stage of diabetes. An acute glucose infusion increases glomerular filtration rate. The involvement of tubuloglomerular feedback response and direct effect of glucose on the afferent arterioles (Af-Arts) have been suggested. However, the signaling pathways to trigger Af-Art dilatation have not been fully identified. Therefore, in the present study we tested our hypothesis that an increase in glucose concentration enhances endothelial nitric oxide synthesis activity and dilates the Af-Arts via glucose transporter-1 (GLUT1) using isolated mouse Af-Arts with perfusion. We isolated and microperfused the Af-Arts from nondiabetic C57BL/6 mice. The Af-Arts were preconstricted with norepinephrine (1 µM). When we switched the d-glucose concentration from low (5 mM) to high (30 mM) in the perfusate, the preconstricted Af-Arts significantly dilated by 37.8 ± 7.1%, but L-glucose did not trigger the dilation. GLUT1 mRNA was identified in microdisserted Af-Arts measured by RT-PCR. Changes in nitric oxide (NO) production in Af-Art were also measured using fluorescent probe when ambient glucose concentration was increased. When the d-glucose concentration was switched from 5 to 30 mM, NO generation in Af-Art was significantly increased by 19.2 ± 6.2% (84.7 ± 4.1 to 101.0 ± 9.3 U/min). l-Glucose had no effect on the NO generation. The GLUT1-selective antagonist 4-[({[4-(1,1-Dimethylethyl)phenyl]sulfonyl}amino)methyl]- N-3-pyridinylbenzamide and the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester blocked the high glucose-induced NO generation and vasodilation. In conclusion, we demonstrated that an increase in glucose concentration dilates the Af-Art by stimulation of the endothelium-derived NO production mediated by GLUT1.