Skeletal muscle microvascular recruitment by physiological hyperinsulinemia precedes increases in total blood flow.

Supraphysiological doses of insulin enhance total limb blood flow and recruit capillaries in skeletal muscle. Whether these processes change in response to physiological hyperinsulinemia is uncertain. To examine this, we infused either saline (n = 6) or insulin (euglycemic clamp, 3.0 mU x min(-1) x kg(-1), n = 9) into anesthetized rats for 120 min. Femoral artery flow was monitored continuously using a Doppler flow probe, and muscle microvascular recruitment was assessed by metabolism of infused 1-methylxanthine (1-MX) and by contrast-enhanced ultrasound (CEU). Insulin infusion raised plasma insulin concentrations by approximately 10-fold. Compared with saline, physiological hyperinsulinemia increased femoral artery flow (1.02 +/- 0.10 vs. 0.68 +/- 0.09 ml/min; P < 0.05), microvascular recruitment (measured by 1-MX metabolism [6.6 +/- 0.5 vs. 4.5 +/- 0.48 nmol/min; P < 0.05] as well as by CEU [167.0 +/- 39.8 vs. 28.2 +/- 13.8%; P < 0.01]), and microvascular flow velocity (beta, 0.14 +/- 0.02 vs. 0.09 +/- 0.02 s(-1)). Subsequently, we studied the time dependency of insulin's vascular action in a second group (n = 5) of animals. Using CEU, microvascular volume was measured at 0, 30, and 90 min of insulin infusion. Insulin augmented microvascular perfusion within 30 min (52.8 +/- 14.8%), and this persisted at 90 min (64.6 +/- 9.9%). Microvascular recruitment occurred without changes to femoral artery flow or beta. We conclude that insulin increases tissue perfusion by recruiting microvascular beds, and at physiological concentrations this precedes increases in total muscle blood flow by 60-90 min.

Physiological hyperinsulinaemia increases intramuscular microvascular reactive hyperaemia and vasomotion in healthy volunteers.

AIMS/HYPOTHESIS: Insulin possesses vasodilatory actions that may be important in regulating its access to insulin-sensitive tissues. Our study aims to directly measure changes in response to insulin in the human skeletal muscle microcirculation. Measurement was by an implanted laser Doppler probe. METHODS: We investigated changes in intramuscular and skin microvascular perfusion in 12 healthy individuals during a hyperinsulinaemic and a control clamp. We determined leg blood flow with plethysmography, finger skin functional capillary recruitment with capillaroscopy, endothelium-(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside, and leg intramuscular reactive hyperaemia and vasomotion with laser Doppler measurements. RESULTS: Compared to the control study, hyperinsulinaemia (416+/-82 pmol/l) caused: (i) an increase in leg blood flow (1.0+/-1.0 vs 0.1+/-0.6 ml.min(-1).100 ml, p<0.05); (ii) an increase in finger skin capillary recruitment (14.9+/-10.1 vs -5.6+/-11.0%, p<0.01); (iii) no change in baseline laser Doppler perfusion either in finger skin or leg muscle; (iv) a tendency to increase acetylcholine-mediated vasodilation (475+/-534 vs 114+/-337%, p=0.07) with no change in sodium-nitroprusside-mediated vasodilation ( p=0.2) in finger skin; (v) an increase in intramuscular reactive hyperaemia (423+/-507 vs 0+/-220%, p<0.01); and (vi) a decrease in time needed to reach peak intramuscular perfusion (-3.6+/-3.0 vs 1.1+/-3.1 s, p<0.01). In addition, hyperinsulinaemia induced an increase in intramuscular vasomotion by increasing the contribution of frequencies between 0.01 and 0.04 Hz ( p<0.05 for all), which probably represents increased endothelial and neurogenic activity. CONCLUSIONS/INTERPRETATION: Physiological hyperinsulinaemia not only stimulates total blood flow and skin microvascular perfusion, but also augments human skeletal muscle microvascular recruitment and vasomotion as detected directly by laser Doppler measurements.