1. The renal effects of insulin may play a central role in the association between insulin resistance, hypertension and hyperuricaemia. After a 2-h baseline period, we investigated the effects of exogenous insulin for 4 h (50 m-units h−1 kg−1) on fractional renal sodium and urate excretion in 13 healthy subjects, using the euglycaemic clamp and lithium clearance technique, and performed a control experiment in eight of the subjects.
2. Insulin caused a decline in both fractional renal sodium excretion, from 1.13 ± 0.41% to 0.88 ± 0.58% (control study: 0.81 ± 0.35 to 1.35 ± 0.49%; P < 0.001, insulin versus control), and fractional renal urate excretion, from 6.72 ± 1.87% to 5.71 ± 2.02% (control study: 7.03 ± 2.06 to 7.05 ± 1.94%; P = 0.085, insulin versus control). The changes in fractional renal sodium and urate excretion were positively correlated (r = 0.71, P < 0.01). Estimated fractional distal sodium reabsorption increased during insulin infusion from 93.7 ± 2.8% to 96.7 ± 1.9% (control study: 95.7 ± 1.5% to 93.6 ± 1.1%; P < 0.001, insulin versus control). Estimated fractional proximal tubular sodium reabsorption fell from 81.0 ± 0.5% to 73.7 ± 4.7% during insulin infusion, but less in the control study (81.5 ± 4.3% to 79.3 ± 4.8%; P = 0.056, insulin versus control). The changes in fractional proximal tubular sodium reabsorption and fractional distal sodium reabsorption during insulin infusion were inversely correlated (r = −0.59, P = 0.03).
3. During the course of the insulin infusion experiment an inverse correlation between the changes in fractional sodium and urate excretion, and the insulin-mediated glucose disposal, became gradually evident (r = −0.73, P < 0.01, and r = −0.71, P < 0.01, respectively; fourth hour of the insulin infusion period).
4. We conclude that exogenous insulin acutely decreases renal sodium and urate excretion, and that this effect is probably exerted at a site beyond the proximal tubule.
