DeFronzo R A, Cooke C R, Andres R, Faloona G R, Davis P J
J Clin Invest. 1975 Apr;55(4):845-55. doi: 10.1172/JCI107996.
The effects of insulin on the renal handling of sodium, potassium, calcium, and phosphate were studied in man while maintaining the blood glucose concentration at the fasting level by negative feedback servocontrol of a variable glucose infusion. In studies on six water-loaded normal subjects in a steady state of water diuresis, insulin was administered i.v. to raise the plasma insulin concentration to between 98 and 193 muU/ml and infused at a constant rate of 2 mU/kg body weight per min over a total period of 120 min. The blood glucose concentration was not significantly altered, and there was no change in the filtered load of glucose; glomerular filtration rate (CIN) and renal plasma flow (CPAH) were unchanged. Urinary sodium excretion (UNaV) decreased from 401 plus or minus 46 (SEM) to 213 plus or minus 18 mueq/min during insulin administration, the change becoming significant (P smaller than 0.02) within the 30-60 min collection period. Free water clearance (CH2O) increased from 10.6 plus or minus 0.6 to 13 plus or minus 0.5 ml/min (P smaller than 0.025); osmolar clearance decreased and urine flow was unchanged. There was no change in plasma aldosterone concentration, which was low throughout the studies, and a slight reduction was observed in plasma glucagon concentration. Urinary potassium (UKV) and phosphate (UPV) excretion were also both decreased during insulin administration; UKV decreased from 66 plus or minus 9 to 21 plus or minus 1 mueq/min (P smaller than 0.005), and tupv decreased from 504 plus or minus 93 to 230 plus or minus 43 mug/min (P smaller than 0.01). The change in UKV was associated with a significant reduction in plasma potassium concentration. There was also a statistically significant but small reduction in plasma phosphate concentration which was not considered sufficient alone to account for the large reduction in UPV. Urinary calcium excretion (UCaV) increased from 126 plus or minus 24 to 200 plus or minus 17 mug/min (P smaller than 0.01). These studies demonstrate a reduction in UNaV associated with insulin administration that occurs in the absence of changes in the filtered load of glucose, glomerular filtration rate, renal blood flow, and plasma aldosterone concentration. The effect of insulin on CH2O suggests that insulin's effect on sodium excretion is due to enhancement of sodium reabsorption in the diluting segment of the distal nephron.
在通过可变葡萄糖输注的负反馈伺服控制将血糖浓度维持在空腹水平的情况下,研究了胰岛素对人体肾脏处理钠、钾、钙和磷酸盐的影响。在对6名处于水利尿稳态的水负荷正常受试者进行的研究中,静脉注射胰岛素以使血浆胰岛素浓度升至98至193微单位/毫升之间,并以2微单位/千克体重每分钟的恒定速率输注120分钟。血糖浓度无明显改变,葡萄糖滤过负荷也无变化;肾小球滤过率(CIN)和肾血浆流量(CPAH)未改变。胰岛素输注期间,尿钠排泄(UNaV)从401±46(标准误)降至213±18微当量/分钟,在30至60分钟的收集期内变化显著(P<0.02)。自由水清除率(CH2O)从10.6±0.6升至13±0.5毫升/分钟(P<0.025);渗透清除率降低,尿流量未变。血浆醛固酮浓度无变化,在整个研究过程中一直较低,血浆胰高血糖素浓度略有降低。胰岛素输注期间尿钾(UKV)和磷酸盐(UPV)排泄也均降低;UKV从66±9降至21±1微当量/分钟(P<0.005),UPV从504±93降至230±43微克/分钟(P<0.01)。UKV的变化与血浆钾浓度的显著降低相关。血浆磷酸盐浓度也有统计学上显著但较小的降低,单独来看不足以解释UPV的大幅降低。尿钙排泄(UCaV)从126±24升至200±17微克/分钟(P<0.01)。这些研究表明,胰岛素输注会使UNaV降低,且这种降低发生在葡萄糖滤过负荷、肾小球滤过率、肾血流量和血浆醛固酮浓度均无变化的情况下。胰岛素对CH2O的影响表明,胰岛素对钠排泄的作用是由于增强了远端肾单位稀释段的钠重吸收。