title: Renal handling of urate and sodium during acute physiological hyperinsulinaemia in healthy subjects.
abstract: 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.
authors.affiliation: Department of Medicine, ICaR-VU, Cardiovascular Research School, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Ter Maaten
authors.forename: A
authors.initials: A
authors.lastname: Voorburg
authors.forename: R J
authors.initials: RJ
authors.lastname: Heine
authors.forename: P M
authors.initials: PM
authors.lastname: Ter Wee
authors.forename: A J
authors.initials: AJ
authors.lastname: Donker
authors.forename: R O
authors.initials: RO
authors.lastname: Gans
mesh_terms: D000293:Adolescent; D000328:Adult; D003401:Creatine / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008094:Lithium / Q000378:metabolism; D008297:Male; D012964:Sodium / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism*
chemical_list: D007328:Insulin; D014527:Uric Acid; D008094:Lithium; D012964:Sodium; D003401:Creatine