Insulin-mediated increases in renal plasma flow are impaired in insulin-resistant normal subjects

Background: Impaired vasodilatation in skeletal muscle is a possible mechanism linking insulin resistance to blood pressure regulation. Increased renal vascular resistance has been demonstrated in the offspring of essential hypertensives. We assessed whether insulin-mediated renal vasodilatation is impaired in insulin-resistant normal subjects. Design: In two groups of 10 insulin-resistant and 10 insulin-sensitive normal subjects, we compared the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU kg^-1 h^-1) on renal plasma flow (RPF) and leg blood flow using the euglycaemic clamp technique, ¹³¹I-labelled Hippuran clearances and venous occlusion plethysmography. Time-control experiments were performed in the same subjects. Results: Whole-body glucose uptake amounted to 4.9 ± 2.1 and 11.0 ± 2.4 mg kg ^-1min^-1 in the insulin-resistant and to 12.7 ± 2.3 and 17.4 ± 2.6 mg kg ^-1min^-1 in the insulin-sensitive subjects during physiological and supraphysiological hyperinsulinaemia, respectively. RPF increased more in insulin-sensitive compared to insulin-resistant subjects during physiological hyperinsulinaemia (13.7 vs. 6.8%, P < 0.05). RPF increased to comparable levels during supraphysiological hyperinsulinaemia. Insulin-mediated changes in leg blood flow did not differ between groups. In the combined group, we found a positive correlation between insulin-mediated glucose uptake and changes in RPF during physiological hyperinsulinaemia (r = 0.57, P = 0.009), whereas insulin-mediated glucose uptake correlated with changes in leg blood flow during supraphysiological hyperinsulinaemia (r = 0.54. P = 0.017). Conclusions: Our results suggest that the sensitivities of the skeletal muscle and renal vascular bed differ for insulin's vasodilatory action. Insulin-mediated increases in RPF are impaired in insulin-resistant but otherwise normal subjects during physiological hyperinsulinaemia.