Direct Evidence for Insulin-Induced Capillary Recruitment in Skin of Healthy Subjects During Physiological Hyperinsulinemia

Abstract

It has been proposed that insulin-mediated changes in muscle perfusion modulate insulin-mediated glucose uptake. However, the putative effects of insulin on the microcirculation that permit such modulation have not been studied in humans. We examined the effects of systemic hyperinsulinemia on skin microvascular function in eight healthy nondiabetic subjects. In addition, the effects of locally administered insulin on skin blood flow were assessed in 10 healthy subjects. During a hyperinsulinemic clamp, we measured leg blood flow with venous occlusion plethysmography, skin capillary density with capillaroscopy, endothelium-(in)dependent vasodilatation of skin microcirculation with iontophoresis of acetylcholine and sodium nitroprusside combined with laser Doppler fluxmetry, and skin vasomotion by Fourier analysis of microcirculatory blood flow. To exclude nonspecific changes in the hemodynamic variables, a time-volume control study was performed. Insulin iontophoresis was used to study the local effects of insulin on skin blood flow. Compared to the control study, systemic hyperinsulinemia caused an increase in leg blood flow (؊0.54 ؎ 0.93 vs. 1.97 ؎ 1.1 ml ⅐ min ؊1 ⅐ dl ؊1 ; P < 0.01), an increase in the number of perfused capillaries in the resting state (؊3.7 ؎ 3.0 vs. 3.4 ؎ 1.4 per mm 2 ; P < 0.001) and during postocclusive reactive hyperemia (؊0.8 ؎ 2.2 vs. 5.1 ؎ 3.7 per mm 2 ; P < 0.001), an augmentation of the vasodilatation caused by acetylcholine (722 ؎ 206 vs. 989 ؎ 495%; P < 0.05) and sodium nitroprusside (618 ؎ 159 vs. 788 ؎ 276%; P < 0.05), and a change in vasomotion by increasing the relative contribution of the 0.01-to 0.02-Hz and 0.4-to 1.6-Hz spectral components (P < 0.05). Compared to the control substance, locally administered insulin caused a rapid increase (ϳ13.5 min) in skin microcirculatory blood flow (34.4 ؎ 42.5 vs. 82.8 ؎ 85.7%; P < 0.05). In conclusion, systemic hyperinsulinemia in skin 1) induces recruitment of capillaries, 2) augments nitric oxide؊mediated vasodilatation, and 3) influences vasomotion. In addition, locally administered insulin 4) induces a rapid increase in total skin blood flow, independent of systemic effects. Diabetes 51: 1515-1522, 2002

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

“…In addition, insulin influenced rhythmic fluctuations of the skin microvasculature (so-called vasomotion) by increasing the relative contribution of endothelial activity. This implies that insulin modulates microcirculatory flow through a mechanism that is dependent on the endothelium [8]. Although the above-mentioned studies are consistent with the concept of an insulinmediated effect on intramuscular microvascular perfusion, such an effect has never been directly assessed in humans by means of intramuscular laser Doppler measurements.…”

“…Leg blood flow was measured by venous occlusion plethysmography (EC6; Hokanson, Bellevue, Wash., USA) in a supine position with the foot elevated [8]. An occlusive cuff was placed proximally around the dominant leg and the strain gauge was placed around the calf at the largest circumference.…”

“…Nailfold capillary studies and iontophoresis studies were performed as described previously [8]. Perfused capillary density was defined as the number of erythrocyteperfused capillaries per square millimetre.…”

“…Microvascular endothelium-(in)dependent vasodilation was determined as described previously [8]. Acetylcholine (1% Miochol, IOLAB, Bourneville Pharma, Braine l'Alleud, Belgium) was delivered on the middle phalanx of the third finger of the non-dominant hand using an anodal current.…”

“…In human skin, we have recently shown that insulin is capable of inducing functional recruitment of capillaries [8]. In addition, insulin influenced rhythmic fluctuations of the skin microvasculature (so-called vasomotion) by increasing the relative contribution of endothelial activity.…”