Gans R O, Bilo H J, Donker A J
Department of Medicine, ICaR-VU Research School Cardiovascular Diseases, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Nephrol Dial Transplant. 1996 May;11(5):794-802. doi: 10.1093/oxfordjournals.ndt.a027401.
Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance hyperinsulinaemia and a high frequency of hypertension. It has recently been shown that insulin exerts a sodium-retaining effect, which is preserved in NIDDM: We sought to determine whether insulin affected renal sodium handling differently in hypertensive and normotensive NIDDM patients.
After a baseline period of 2 h, eight normotensive (N-) NIDDM patients and eight NIDDM patients with hypertension (H-) underwent a euglycaemic clamp with infusion of two sequential doses of insulin (50 and 500 mU/kg/h) or vehicle (time control) during 2-h periods each. Fractional clearances of sodium and lithium were determined according to standard methods. Fractional lithium clearance was used to assess segmental tubular sodium handling.
Insulin induced similar decrements in fractional sodium excretion (N-NIDDM: 43+/-5.9 and 57+/-9.1%,H-N IDDM: 48+/-16.4 and 62+/-12.5%, low and high insulin dose respectively). Distal tubular sodium absorption increased simultaneously. A fall in fractional proximal sodium reabsorption was observed in N-NIDDM (4.4+/-2.7 and 29.8+/-5.1%, low and high insulin dose respectively), which was attenuated in H-NIDDM (-5.0+/-7.3 and -2.1+/-13.9% respectively). The latter appeared to be related to a defective atrial natriuretic factor (ANF) and renal cyclic GMP response. A modest decrease in blood pressure occurred during insulin infusion that was not related to changes in ANF or FeLi.
The findings suggest that insulin-induced sodium retention may contribute to hypertension in NIDDM if the homeostatic response to offset this effect fails.
非胰岛素依赖型糖尿病（NIDDM）的特征为胰岛素抵抗、高胰岛素血症和高血压的高发病率。最近研究表明胰岛素具有保钠作用，在NIDDM患者中此作用依然存在：我们试图确定胰岛素对高血压和血压正常的NIDDM患者肾脏处理钠的方式是否有不同影响。
在2小时的基线期后，8名血压正常（N-）的NIDDM患者和8名高血压（H-）的NIDDM患者分别在两个2小时时间段内接受了正常血糖钳夹试验，期间输注两剂连续剂量的胰岛素（50和500 mU/kg/h）或赋形剂（时间对照）。根据标准方法测定钠和锂的分数清除率。分数锂清除率用于评估肾小管节段性钠处理情况。
胰岛素导致分数钠排泄出现相似程度的下降（N-NIDDM组：分别为43±5.9%和57±9.1%，低剂量和高剂量胰岛素时；H-NIDDM组：分别为48±16.4%和62±12.5%）。远端肾小管钠吸收同时增加。在N-NIDDM组中观察到分数近端钠重吸收下降（分别为4.4±2.7%和29.8±5.1%，低剂量和高剂量胰岛素时），而在H-NIDDM组中这种下降减弱（分别为-5.0±7.3%和-2.1±13.9%）。后者似乎与心房利钠因子（ANF）和肾环磷酸鸟苷反应缺陷有关。胰岛素输注期间血压出现适度下降，这与ANF或分数锂清除率的变化无关。
研究结果表明，如果抵消这种作用的稳态反应失败，胰岛素诱导的钠潴留可能导致NIDDM患者发生高血压。
