Effect of insulin on renal sodium and uric acid handling in essential hypertension
Effect of insulin on renal sodium and uric acid handling in essential hypertension
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DOI：
10.1016/0895-7061(96)00098-2
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发表时间：
1996-08-01
影响因子：
3.2
通讯作者：
Ferrannini, E
中科院分区：
文献类型：
--
作者：
Muscelli, E;Natali, A;Ferrannini, E
在正常人中，胰岛素减少钠、钾和尿酸的尿排泄。我们检测了胰岛素抵抗性高血压患者胰岛素的肾脏效应是否改变。在37例原发性高血压患者中，我们测量了生理性正常血糖高胰岛素血症（通过使用胰岛素钳夹技术，胰岛素输注速率为6 pmol/min/kg）时尿钠、钾和尿酸排泄的变化。葡萄糖代谢率平均为26.6 ± 1.5 μ mol/min/kg，比血压正常的对照组（33.1 ± 2.1 μ mol/min/kg，P = 0.015）低20%。在基础状态下，男性空腹血浆尿酸浓度高于女性（P < .001），与体重指数呈正相关（r = 0.38，P = 0.02），腰/臀比（r = 0.35，P <0.05），血清甘油三酯水平（r = 0.59，P = .0001），与HDL胆固醇浓度（r =-0.59，P = .0001）和葡萄糖代谢率（r = 0.42，P < .01）呈负相关。另一方面，尿酸清除率与体重指数（r = 0.41，P = 0.01）、血浆尿酸（r = 0.65，P <0.0001）和甘油三酯浓度（r = 0.39，P <0.02）呈负相关，与高密度脂蛋白胆固醇水平（r = 0.52，P <0.001）呈正相关。在胰岛素输注期间，血压、血浆尿酸和钠浓度以及肌酐清除率没有变化。相反，高胰岛素血症导致尿酸的尿排泄显著减少（2.67 +/- 0.12至1.86 +/- .14 μ mol/min/1.73 m（2），P = .0001），钠（184 +/- 12至137 +/- 14 μ mol/l/1.73 m（2），P = .0001）和钾（81 +/- 7至48 +/- 4 μ mol/min/1.73 m（2），P = .0001）。无论是在绝对值（清除率和排泄率分数）和累积量方面，这些变化与血压正常受试者中发现的变化相似。胰岛素诱导的尿酸盐排泄的变化与钠排泄的相应变化相关（r = 0.55，P <0.0001）。在高血压患者中，较高的尿酸水平和较低的肾脏尿酸清除率与胰岛素抵抗和血脂异常相关。尽管葡萄糖代谢存在胰岛素抵抗，但急性生理性高胰岛素血症可导致这些患者正常的抗钠尿、抗钾尿和抗尿酸尿。
In normal subjects, insulin decreases the urinary excretion of sodium, potassium, and uric acid. We tested whether these renal effects of insulin are altered in insulin resistant hypertension. In 37 patients with essential hypertension, we measured the changes in urinary excretion of sodium, potassium, and uric acid in response to physiological euglycemic hyperinsulinemia (by using the insulin clamp technique at an insulin infusion rate of 6 pmol/min/kg). Glucose disposal rate averaged 26.6 +/- 1.5 mu mol/min/kg, ie, 20% lower than in normotensive controls (33.1 +/- 2.1 mu mol/min/kg, P = .015). In the basal state, fasting plasma uric acid concentrations were higher in men than women (P < .001), were positively related to body mass index (r = 0.38, P = .02), waist/hip ratio (r = 0.35, P < .05), and serum triglyceride levels (r = 0.59, P = .0001), and negatively related to HDL cholesterol concentrations (r = -0.59, P = .0001) and glucose disposal rate (r = 0.42, P < .01). Uric acid clearance, on the other hand, was inversely related to body mass index (r = 0.41, P = .01), plasma uric acid (r = 0.65, P < .0001) and triglyceride concentrations (r = 0.39, P < .02), and directly related to HDL cholesterol levels (r = 0.52, P < .001). During insulin infusion, blood pressure, plasma uric acid and sodium concentration, and creatinine clearance did not change. In contrast, hyperinsulinemia caused a significant decrease in the urinary excretion of uric acid (2.67 +/- 0.12 to 1.86 +/- .14 mu mol/min/1.73 m(2), P = .0001), sodium (184 +/- 12 to 137 +/- 14 mu mol/l/1.73 m(2), P = .0001), and potassium (81 +/- 7 to 48 +/- 4 mu mol/min/1.73 m(2), P = .0001). Both in absolute terms (clearance and fractional excretion rates) and percentagewise, these changes were similar to those found in normotensive subjects. Insulin-induced changes in urate excretion were coupled (r = 0.55, P < .0001) to the respective changes in sodium excretion. In hypertensive patients, higher uric acid levels and lower renal urate clearance rates cluster with insulin resistance and dyslipidemia. Despite insulin resistance of glucose metabolism, acute physiological hyperinsulinemia causes normal antinatriuresis, antikaliuresis, and antiuricosuria in these patients.