title: Insulin-induced changes in skeletal muscle microvascular perfusion are dependent upon perivascular adipose tissue in women.
abstract: OBJECTIVE
  Obesity increases the risk of cardiovascular disease and type 2 diabetes, partly through reduced insulin-induced microvascular vasodilation, which causes impairment of glucose delivery and uptake. We studied whether perivascular adipose tissue (PVAT) controls insulin-induced vasodilation in human muscle, and whether altered properties of PVAT relate to reduced insulin-induced vasodilation in obesity.
  
  
  METHODS
  Insulin-induced microvascular recruitment was measured using contrast enhanced ultrasound (CEU), before and during a hyperinsulinaemic-euglycaemic clamp in 15 lean and 18 obese healthy women (18-55 years). Surgical skeletal muscle biopsies were taken on a separate day to study perivascular adipocyte size in histological slices, as well as to study ex vivo insulin-induced vasoreactivity in microvessels in the absence and presence of PVAT in the pressure myograph. Statistical mediation of the relation between BMI and microvascular recruitment by PVAT was studied in a mediation model.
  
  
  RESULTS
  Obese women showed impaired insulin-induced microvascular recruitment and lower metabolic insulin sensitivity compared with lean women. Microvascular recruitment was a mediator in the association between obesity and insulin sensitivity. Perivascular adipocyte size, determined in skeletal muscle biopsies, was larger in obese than in lean women, and statistically explained the difference in microvascular recruitment between obese and lean women. PVAT from lean women enhanced insulin-induced vasodilation in isolated skeletal muscle resistance arteries, while PVAT from obese women revealed insulin-induced vasoconstriction.
  
  
  CONCLUSIONS
  PVAT from lean women enhances insulin-induced vasodilation and microvascular recruitment whereas PVAT from obese women does not. PVAT adipocyte size partly explains the difference in insulin-induced microvascular recruitment between lean and obese women.
authors.affiliation: Department of Internal Medicine, VU University Medical Center and Institute for Cardiovascular Research, VU University Medical Center, room 4A72, Postbus 7057, 1007 MB, Amsterdam, the Netherlands, r.meijer@vumc.nl.
authors.forename: Rick I
authors.initials: RI
authors.lastname: Meijer
authors.forename: Erik H
authors.initials: EH
authors.lastname: Serné
authors.forename: H Ibrahim
authors.initials: HI
authors.lastname: Korkmaz
authors.forename: Donald L
authors.initials: DL
authors.lastname: van der Peet
authors.forename: Michiel P
authors.initials: MP
authors.lastname: de Boer
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.forename: Victor W M
authors.initials: VW
authors.lastname: van Hinsbergh
authors.forename: John S
authors.initials: JS
authors.lastname: Yudkin
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Etto C
authors.initials: EC
authors.lastname: Eringa
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000502:physiology; D000293:Adolescent; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D055806:Microvessels / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D007328:Insulin