TY - JOUR
T1 - Direct evidence for insulin-induced capillary recruitment in skin of healthy subjects during physiological hyperinsulinemia
AU - Serné, Erik H.
AU - Ijzerman, Richard G.
AU - Gans, Reinold O.B.
AU - Nijveldt, Robin
AU - De Vries, Greetje
AU - Evertz, Reinder
AU - Donker, Ab J.M.
AU - Stehouwer, Coen D.A.
PY - 2002/1/1
Y1 - 2002/1/1
N2 - 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 · min-1 · 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 mm2; P < 0.001) and during postocclusive reactive hyperemia (-0.8 ± 2.2 vs. 5.1 ± 3.7 per mm2; 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 (∼13.5 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.
AB - 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 · min-1 · 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 mm2; P < 0.001) and during postocclusive reactive hyperemia (-0.8 ± 2.2 vs. 5.1 ± 3.7 per mm2; 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 (∼13.5 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.
UR - http://www.scopus.com/inward/record.url?scp=0036316948&partnerID=8YFLogxK
U2 - https://doi.org/10.2337/diabetes.51.5.1515
DO - https://doi.org/10.2337/diabetes.51.5.1515
M3 - Article
C2 - 11978650
SN - 0012-1797
VL - 51
SP - 1515
EP - 1522
JO - Diabetes
JF - Diabetes
IS - 5
ER -