Effects of insulin on renal haemodynamics and sodium handling in normal subjects

Abstract

Diabetic patients treated with insulin injected subcutaneously are characterized by peripheral hyperinsulinaemia and an increased mass of total body exchangeable sodium. We hypothesized that this may cause, at least in part, the glomerular hyperfiltration seen in the diabetic state. Six normal subjects were studied on 2 days in random order. Day A: Basal state for 40 min, hyperinsulinaemic eugly-caemic clamp for 1 h (insulin infusion rate 2 mU kg^-' min^-1 and 50% glucose infusion) and hyperinsulinaemic euglycaemic clamp combined with volume expansion (2 1 isotonic sodium chloride) for 2 h. Day B: as day A, but without insulin and glucose infusion.

During combined volume expansion and hyperinsulinaemia an increase in glomerular filtration rate (GFR) (128± 6 vs 117 ± 8 ml min^-1 1.73 m^-2, p<0.01) and lithium clearance (CLi) (50 ± 4 vs 33 ± 5 ml min^-1 1.73 m^-2, p<0.01) was observed compared with basal conditions. GFR and C_Li were unchanged during day B. Insulin infusion reduced renal sodium excretion. Absolute proximal tubular reabsorption was unchanged on both days. Insulin infusion without volume expansion caused a decrease of 24% in the fractional distal sodium excretion. Superimposed volume expansion and the concomitant increase in GFR and C_Li was accompanied by a subsequent enhanced fractional distal sodium excretion of 27%. The changes in plasma concentrations of aldosterone, renin, angiotensin II, atrial natriuretic peptide and catecholamines did not explain the differences in GFR.

An increase in GFR of 10%, comparable with that observed in diabetic patients, was induced by combined hyperinsulinaemia and volume expansion in euglycaemic normal subjects. The enhanced GFR is probably a compensatory response to the sodium retention induced by the action of insulin on the distal tubules.

Key Words:

• glomerular filtration rate
• hyperinsulinaemia
• lithium clearance
• renal hormones
• sodium handling
• volume expansion