Department of Clinical Physiology and Nuclear Medicine, Bispebjerg and Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, Denmark.
Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
J Clin Endocrinol Metab. 2019 Jul 1;104(7):2509-2519. doi: 10.1210/jc.2019-00004.
We have previously demonstrated that glucagon-like peptide-1 (GLP-1) does not affect renal hemodynamics or function under baseline conditions in healthy participants and in patients with type 2 diabetes mellitus. However, it is possible that GLP-1 promotes natriuresis under conditions with addition of salt and water to the extracellular fluid. The current study was designed to investigate a possible GLP-1-renal axis, inducing natriuresis in healthy, volume-loaded participants.
Under fixed sodium intake, eight healthy men were examined twice in random order during a 3-hour infusion of either GLP-1 (1.5 pmol/kg/min) or vehicle together with an intravenous infusion of 0.9% NaCl. Timed urine collections were conducted throughout the experiments. Renal plasma flow (RPF), glomerular filtration rate (GFR), and uptake and release of hormones and ions were measured via Fick's principle.
During GLP-1 infusion, urinary sodium and osmolar excretions increased significantly compared with vehicle. Plasma renin levels decreased similarly on both days, whereas angiotensin II (ANG II) levels decreased significantly only during GLP-1 infusion. RPF and GFR remained unchanged on both days.
In volume-loaded participants, GLP-1 induces natriuresis, probably brought about via a tubular mechanism secondary to suppression of ANG II, independent of renal hemodynamics, supporting the existence of a GLP-1-renal axis.
我们之前已经证明，在健康参与者和 2 型糖尿病患者中，胰高血糖素样肽-1（GLP-1）在基础条件下不会影响肾脏的血液动力学或功能。然而，在向细胞外液中添加盐和水的情况下，GLP-1 可能会促进尿钠排泄。本研究旨在研究健康、容量负荷增加的参与者中可能存在的 GLP-1-肾脏轴，以诱导尿钠排泄。
在固定的钠摄入量下，8 名健康男性在随机顺序下两次接受 3 小时的 GLP-1（1.5 pmol/kg/min）或载体输注，同时静脉输注 0.9%NaCl。整个实验过程中进行定时尿液收集。通过 Fick 原理测量肾血浆流量（RPF）、肾小球滤过率（GFR）以及激素和离子的摄取和释放。
与载体相比，GLP-1 输注期间尿钠和尿渗透压排泄显著增加。在两天内，血浆肾素水平相似地下降，而血管紧张素 II（ANG II）水平仅在 GLP-1 输注期间显著下降。在两天内，RPF 和 GFR 均保持不变。
在容量负荷增加的参与者中，GLP-1 诱导尿钠排泄，可能是通过抑制 ANG II 引起的肾小管机制实现的，与肾脏血液动力学无关，支持 GLP-1-肾脏轴的存在。
