Pelikánová T, Pinsker P, Smrcková I, Stribrná L, Dryáková M
Institute for Clinical and Experimental Medicine, Postgraduate Medical School, Prague, Czech Republic.
J Diabetes Complications. 1998 Sep-Oct;12(5):264-72. doi: 10.1016/s1056-8727(98)00002-6.
The aim of the study was to evaluate the role of urinary kallikrein in the regulation of renal hemodynamics and sodium handling in insulin-dependent diabetes mellitus (IDDM), and to test the effect of acutely induced hyperglycemia. Urinary kallikrein excretion was evaluated (1) under basal conditions and after stimulation with i.v. furosemide (0.5 mg x kg(-1)), (2) during glycemic clamp-induced eu- and hyperglycemia (5 and 12 mmol/L) and, (3) during time-controlled euglycemia in 21 short-term IDDM patients without microalbuminuria and in 18 weight-, age- and gender-matched healthy controls. Sodium excretion and renal hemodynamics using the clearances of inulin and para-amino-hippuric acid were measured during examinations in both groups. The baseline urinary kallikrein excretion during clamp-induced euglycemia was comparable in diabetic and control subjects (10.89+/-5.98 versus 10.38+/-3.73 mUE x min(-1)), whereas it was decreased in the baseline for furosemide (5.77+/-3.22 versus 10.9+/-3.7 mUE x min(-1); p < 0.01) and even after furosemide administration (12.0+/-1.6 versus 21.3+/-2.0 mUE x min(-1); p < 0.01) while the patients were hyperglycemic. During intravenous dextrose-induced hyperglycemia, the urinary kallikrein excretion significantly declined in diabetic patients (10.89+/-5.98 versus 5.45+/-0.88 mUE x min(-1); p < 0.01), whereas it did not change in controls (10.38+/-3.73 versus 12.55+/-5.47 mUE x min(-1)). A decrease in the fractional excretion of sodium and an attenuated rise in natriuresis after furosemide administration have been found in diabetic compared to control subjects. There were no significant relationships between kallikrein excretion and (1) renal hemodynamics, which was comparable in both groups, or (2) plasma renin activity, plasma and urine aldosterone and cortisol. We conclude that short-term IDDM without renal hemodynamic alterations is associated with decreased basal and furosemide-stimulated kallikrein excretion, which is directly related to the blood glucose level. The decreased activity of the renal kallikrein-kinin system might be involved in the increased tendency to sodium retention in diabetic patients.
本研究的目的是评估尿激肽释放酶在胰岛素依赖型糖尿病（IDDM）患者肾血流动力学调节和钠代谢中的作用，并测试急性诱导高血糖的影响。评估尿激肽释放酶排泄情况：（1）在基础条件下以及静脉注射速尿（0.5mg·kg⁻¹）刺激后；（2）在血糖钳夹诱导的正常血糖和高血糖（5和12mmol/L）期间；（3）在21例无微量白蛋白尿的短期IDDM患者以及18例体重、年龄和性别匹配的健康对照者的时间控制正常血糖期间。两组在检查期间均测量了使用菊粉和对氨基马尿酸清除率的钠排泄和肾血流动力学。在血糖钳夹诱导的正常血糖期间，糖尿病患者和对照者的基线尿激肽释放酶排泄相当（10.89±5.98对10.38±3.73mUE·min⁻¹），而在速尿基线时其排泄减少（5.77±3.22对10.9±3.7mUE·min⁻¹；p<0.01），甚至在患者高血糖时给予速尿后也是如此（12.0±1.6对21.3±2.0mUE·min⁻¹；p<0.01）。在静脉注射葡萄糖诱导的高血糖期间，糖尿病患者的尿激肽释放酶排泄显著下降（10.89±5.98对5.45±0.88mUE·min⁻¹；p<0.01），而对照者则无变化（10.38±3.73对12.55±5.47mUE·min⁻¹）。与对照者相比，糖尿病患者在给予速尿后钠排泄分数降低且利钠作用减弱。在激肽释放酶排泄与（1）两组相当的肾血流动力学，或（2）血浆肾素活性、血浆和尿醛固酮及皮质醇之间均无显著关系。我们得出结论，无肾血流动力学改变的短期IDDM与基础和速尿刺激的激肽释放酶排泄减少有关，这与血糖水平直接相关。肾激肽释放酶-激肽系统活性降低可能参与了糖尿病患者钠潴留倾向增加的过程。
