Journal Article

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

Greetje de Vries, Reinder Evertz, Ab J.M. Donker, Reinold O.B. Gans, Coen D.A. Stehouwer, Erik H. Serné, Robin Nijveldt, Richard G. IJzerman

2002

Overview

Direct Evidence for Insulin-Induced Capillary Recruitment in Skin of Healthy Subjects During Physiological Hyperinsulinemia Erik H. Serné 1 2 , Richard G. IJzerman 1 2 , Reinold O.B. Gans 3 , Robin Nijveldt 1 , Greetje de Vries 1 , Reinder Evertz 1 , Ab J.M. Donker 1 2 and Coen D.A. Stehouwer 1 2 1 Department of Medicine, Academic Hospital Vrije Universiteit, Amsterdam, the Netherlands 2 Institute for Cardiovascular Research-Vrije Universiteit, Amsterdam, the Netherlands 3 Department of Medicine, University Hospital Groningen, Groningen, the Netherlands 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 · 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 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 (∼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. Footnotes Address correspondence and reprint requests to Dr. C.D.A. Stehouwer, Department of Medicine, Academic Hospital Vrije Universiteit, De Boelelaan 1117, P.O. Box 5057, 1007 MB, Amsterdam, the Netherlands. E-mail: cda.stehouwer{at}vumc.nl . Received for publication 17 January 2001 and accepted in revised form 15 February 2002. CV, coefficient of variation; DBP, diastolic blood pressure; M, whole-body glucose uptake; MAP, mean arterial pressure; M/I, whole-body glucose uptake per unit of plasma insulin concentration; PRH, postocclusive reactive hyperemia; PU, arbitrary perfusion units. DIABETES

• Publisher: American Diabetes Association
• Subject: Acetylcholine - administration & dosage / Adult / Biological and medical sciences / Biological transport / Capillaries - drug effects / Diabetes / Diabetes research / Endocrine pancreas / Endothelium, Vascular - physiology / Female / Fundamental and applied biological sciences. Psychology / Humans / Hyperinsulinism - chemically induced / Hyperinsulinism - physiopathology / Hypoglycemic Agents - administration & dosage / Insulin / Insulin - administration & dosage / Iontophoresis / Laser-Doppler Flowmetry / Male / Measurement / Morphology. Functional localizations / Nitroprusside - administration & dosage / Regional blood flow / Regional Blood Flow - drug effects / Skin - blood supply / Vasodilation - drug effects / Vasodilator Agents - administration & dosage / Vertebrates: endocrinology