Effect of hyperinsulinaemia on renal function and nitrate/nitrite excretion in healthy subjects.
1. In addition to its metabolic actions, insulin acts as a vasodilator in certain vascular beds, such as skeletal muscle. It has been shown that this effect is mediated by endothelium-derived nitric oxide (NO). Unlike in the skeletal muscle, insulin-NO interactions in the kidney, another major site of insulin action, have been less studied. The aim of the present study was to explore the role of NO in renal effects of hyperinsulinaemia in healthy subjects. 2. Changes in renal function and urinary nitrate/nitrite (NO2-/NO3-; Griess method) levels as a marker of renal production of NO were assessed during euglycaemic hyperinsulinaemic clamp and compared with normoinsulinaemic isovolaemic conditions (administration of the same amount of insulin/glucose-free vehicle) in 10 healthy male volunteers. 3. Hyperinsulinaemia was associated with a decrease in renal excretion of stable metabolites of NO (mean (+/- SEM) 0.56 +/- 0.12 vs 0.38 +/- 0.05 mumol/min, respectively; P < 0.05). In contrast, administration of the same volume of insulin-free vehicle resulted in elevation of urinary NO2-/NO3- (P < 0.05). The changes in renal sodium handling followed a similar pattern as changes in the renal excretion of NO2-/NO3- with a significantly different response to hyperinsulinaemia when compared with normoinsulinaemia (F = 12.2; P < 0.001). The mean arterial pressure, blood levels of low-density lipoprotein-cholesterol and free fatty acids, possible factors influencing renal and systemic NO production, remained constant throughout both experiments. 4. These results suggest that hyperinsulinaemia is associated, in healthy males, with a decrease in renal generation of NO. In contrast, mild volume expansion with insulin-free vehicle resulted in increased excretion of NO metabolites. This insulin-induced attenuation of renal NO synthesis may contribute to the anti-natriuretic actions of insulin.
Komers
R
R
Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. komersr@ohsu.edu
Pelikanová
T
T
Kazdová
L
L
D000328:Adult; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000503:physiopathology / Q000652:urine*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009318:Natriuresis; D009566:Nitrates / Q000097:blood / Q000652:urine*; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000097:blood / Q000652:urine*
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide