title: Angiotensin II enhances insulin-stimulated whole-body glucose disposal but impairs insulin-induced capillary recruitment in healthy volunteers.
abstract: BACKGROUND
  Angiotensin II (AngII) increases insulin-mediated glucose uptake in healthy individuals. The underlying mechanisms are undefined. AngII may increase glucose uptake through a direct effect on muscle cell insulin signaling or through increasing insulin delivery to muscle cells through effects on the microvasculature.
  
  
  OBJECTIVE
  Our objective was to determine whether AngII increases insulin-mediated glucose uptake through effects on insulin-induced capillary recruitment.
  
  
  METHODS
  We examined the effects of AngII on hyperinsulinemia-induced capillary density by measuring skin capillary density, capillary recruitment, and capillary density during venous congestion in 18 healthy subjects in the basal state, during systemic hyperinsulinemia, and during hyperinsulinemia with coinfusion of AngII or phenylephrine (pressor control). In addition, whole-body glucose uptake and blood pressure were measured.
  
  
  RESULTS
  Capillaroscopy data of 13 subjects were available for analysis. Compared with the basal state, hyperinsulinemia increased baseline capillary density (51.5+/-9.0 vs. 55.2+/-10.8 n/mm2, P<0.01), capillary recruitment (67.8+/-6.8 vs. 70.6+/-7.5 n/mm2, P<0.05), and capillary density during venous congestion (78.5+/-12.0 vs. 80.3+/-12.0 n/mm2, P<0.01). Infusion of AngII, but not phenylephrine, reduced insulin-induced capillary recruitment (69.3+/-8.6 vs. 65.2+/-8.0 n/mm2, P<0.05) and capillary density during venous congestion (79.7+/-15.3 vs. 73.9+/-12.1, P<0.05) while enhancing glucose uptake [2.40+/-0.7 vs. 2.68+/-0.6 (mg/kg.min per pmol/l)x100, P<0.01)] (n=18).
  
  
  CONCLUSIONS
  AngII increases insulin-mediated glucose uptake in healthy individuals. This increase was probably not related to increases in microvascular perfusion because infusion of AngII during hyperinsulinemia reduced insulin-mediated skin capillary recruitment. Additional studies are needed to investigate whether AngII directly affects insulin delivery through increasing insulin transport across the microvasculature.
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. a.jonk@intmed.unimaas.nl
authors.forename: Amy M
authors.initials: AM
authors.lastname: Jonk
authors.forename: Alfons J H M
authors.initials: AJ
authors.lastname: Houben
authors.forename: Nicolaas C
authors.initials: NC
authors.lastname: Schaper
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: Erik H
authors.initials: EH
authors.lastname: Serné
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D001794:Blood Pressure; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006339:Heart Rate; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D020678:Microscopic Angioscopy; D008875:Middle Aged
chemical_list: D007328:Insulin; D000804:Angiotensin II; D005947:Glucose