Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlate with salt sensitivity in normal subjects

Abstract

Background. Insulin induces increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects could link insulin resistance to blood-pressure elevation and salt sensitivity. Methods. We assessed the relationship between the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU/kg/h) on renal sodium handling, and insulin sensitivity and salt sensitivity using the euglycaemic clamp technique and clearances of [131I]hippuran, [125I]iothalamate, sodium, and lithium in 20 normal subjects displaying a wide range of insulin sensitivity. Time-control experiments were performed in the same subjects. Salt sensitivity was determined using a diet method. Results. During the successive insulin infusions, GFR increased by 5.9% (P = 0.003) and 10.9% (P < 0.001), while fractional sodium excretion decreased by 34 and 50% (both P < 0.001). Distal tubular sodium reabsorption increased and proximal tubular sodium reabsorption decreased. Insulin sensitivity correlated with changes in GFR during physiological (r = 0.60, P = 0.005) and supraphysiological (r = 0.58, P = 0.007) hyperinsulinaemia, but not with changes in proximal tubular sodium reabsorption. Salt sensitivity correlated with changes in proximal tubular sodium reabsorption (r= 0.49, P = 0.028), but not in GFR, during physiological hyperinsulinaemia. Neither insulin sensitivity or salt sensitivity correlated with changes in overall fractional sodium excretion. Conclusions. Insulin sensitivity and salt sensitivity correlate with changes in different elements of renal sodium handling, but not with overall sodium excretion, during insulin infusion. The relevance for blood pressure regulation remains to be proved.