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

Background Impaired vasodilatation in skeletal muscle is a possible mechani sm linking insulin resistance to blood pressure regulation. Increased renal vascular resistance has been demonstrated in the offspring of essential hy pertensives. We assessed whether insulin-mediated renal vasodilatation is i mpaired in insulin-resistant normal subjects. Design In two groups of 10 insulin-resistant and 10 insulin-sensitive norma l subjects, we compared the effects of sequential physiological and supraph ysiological insulin dosages (50 and 150 mU kg(-1) h(-1)) on renal plasma fl ow (RPF) and leg blood flow using the euglycaemic clamp technique, I-131-la belled Hippuran clearances and venous occlusion plethysmography. Time-contr ol 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 (-1)min(-1) in the insulin-resistant and to 12.7 +/- 2.3 and 17.4 +/- 2.6 mg kg (-1)min(-1) in the insulin-sensitive subjects during physiologic al and supraphysiological hyperinsulinaemia, respectively. RPF increased mo re in insulin-sensitive compared to insulin-resistant subjects during physi ological hyperinsulinaemia (13.7 vs. 6.8%, P < 0.05). RPF increased to comp arable levels during supraphysiological hyperinsulinaemia. Insulin-mediated changes in leg blood flow did not differ between groups. In the combined g roup, we found a positive correlation between insulin-mediated glucose upta ke 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 musc le 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.