DIRECT VASODILATOR EFFECTS OF PHYSIOLOGICAL HYPERINSULIN-AEMIA IN HUMAN SKELETAL-MUSCLE

Systemic hyperinsulinaemia induces vasodilatation in human skeletal mu scle. This effect is gradual in onset, and at low insulin levels not m aximal until at least 3 h. To investigate whether the vasodilator resp onse to insulin results from a direct vascular effect, we infused insu lin directly into the cannulated brachial artery (perfused forearm tec hnique) in a total of 30 experiments in 20 healthy, lean, normotensive volunteers. Local, intra-arterial, infusion of insulin (180 min, 0.3 mU dL(-1) forearm volume min(-1), n = 15, forearm venous insulin conce ntration approximately 540 pmol L(-1)) induced a gradual increase in f orearm blood flow (FBF; venous occlusion plethysmography) from 1.86 +/ - 0.17 to 3.64 +/- 0.64 mL dL(-1) min(-1) after 180 min (ANOVA P < 0.0 01). Percentage increases in FBF after 60, 120 and 180 min averaged 14 .4 +/- 5.9, 59.4 +/- 25.5 and 124.6 +/- 51.2% respectively. Forearm gl ucose uptake increased from 0.24 +/- 0.05 to a maximum of 1.98 +/- 0.2 8 mu mol dL(-1) min (P < 0.001). Furthermore, insulin infusion increas ed forearm lactate release and potassium uptake. In 10 out of these 15 individuals, the forearm glucose uptake was further increased in a se cond, separate, repeat experiment with concomitant intra-arterial infu sion of glucose 5% (0.2 mL dL(-1) min(-1)), resulting in forearm venou s glucose concentrations of approximately 15 mmol L(-1). This combined infusion achieved a similar vasodilator response to the infusion of i nsulin alone. The individual vascular responses of the two paired expe riments showed a strong correlation (r = 0.87, P < 0.01). In five subj ects time and vehicle control experiments were performed, showing no c hanges in FBF or metabolism during the 180 min. We conclude that the s low vasodilator response to insulin (as observed during systemic infus ion) can, at least partly, be explained by a direct vascular effect of insulin. Insulin-mediated skeletal muscle glucose uptake precedes thi s effect, but seems not to be an important determinant of the vasodila tor response to insulin.