DeFronzo · The Journal of clinical investigation 1975 · Before-after interventional physiological study · n=6

The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man.

Cited 1124 times in the scientific literature.

Level 4 - case-series / case-control

Uncontrolled before-after physiological intervention study in healthy volunteers

PubMed 1120786 · doi:10.1172/JCI107996 · record verified 2026-08-29

What was done

Six water-loaded healthy human subjects in a steady state of water diuresis were infused with intravenous insulin at a constant rate of 2 mU/kg/min for 120 minutes (achieving plasma insulin concentrations of 98 to 193 µU/ml). Fasting blood glucose was held constant using feedback-controlled variable glucose infusion. Investigators measured glomerular filtration rate (inulin clearance), renal plasma flow (PAH clearance), free water clearance, plasma aldosterone, plasma glucagon, and urinary excretion rates of sodium, potassium, phosphate, and calcium.

What was found

Blood glucose, filtered glucose load, inulin clearance, PAH clearance, and plasma aldosterone were unchanged throughout the infusion. Urinary sodium excretion decreased from 401 ± 46 to 213 ± 18 µeq/min (P < 0.02), with significance reached within 30–60 minutes. Free water clearance increased from 10.6 ± 0.6 to 13 ± 0.5 ml/min (P < 0.025) while urine flow was unchanged and osmolar clearance decreased. Urinary potassium excretion decreased from 66 ± 9 to 21 ± 1 µeq/min (P < 0.005) alongside a drop in plasma potassium. Urinary phosphate excretion decreased from 504 ± 93 to 230 ± 43 µg/min (P < 0.01) alongside a small decrease in plasma phosphate. Urinary calcium excretion increased from 126 ± 24 to 200 ± 17 µg/min (P < 0.01). A slight reduction in plasma glucagon was observed.

Why it matters

This study provides classic human evidence that insulin directly promotes distal renal tubular sodium reabsorption independently of changes in filtered glucose load, renal hemodynamics, or aldosterone secretion.

Limits

The study is limited by a very small sample size (n = 6) and the absence of a time-matched vehicle-control or sham-infusion arm. Experiments were conducted under non-physiological conditions of continuous water diuresis, and measurements reflect only short-term (120-minute) acute responses.

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