title: Contrast-enhanced ultrasound assessment of impaired adipose tissue and muscle perfusion in insulin-resistant mice.
abstract: BACKGROUND
  In diabetes mellitus, reduced perfusion and capillary surface area in skeletal muscle, which is a major glucose storage site, contribute to abnormal glucose homeostasis. Using contrast-enhanced ultrasound, we investigated whether abdominal adipose tissue perfusion is abnormal in insulin resistance and correlates with glycemic control.
  
  
  RESULTS
  Contrast-enhanced ultrasound perfusion imaging of abdominal adipose tissue and skeletal muscle was performed in obese insulin resistance (db/db) mice at 11 to 12 or 14 to 16 weeks of age and in control lean mice. Time-intensity data were analyzed to quantify microvascular blood flow (MBF) and capillary blood volume (CBV). Blood glucose response for 1 hour was measured after insulin challenge (1 U/kg, IP). Compared with control mice, db/db mice at 11 to 12 and 14 to 16 weeks had a higher glucose concentration area under the curve after insulin (11.8±2.8, 20.6±4.3, and 28.4±5.9 mg·min/dL [×1000], respectively; P=0.0002) and also had lower adipose MBF (0.094±0.038, 0.035±0.010, and 0.023±0.01 mL/min per gram; P=0.0002) and CBV (1.6±0.6, 1.0±0.3, and 0.5±0.1 mL/100 g; P=0.0017). The glucose area under the curve correlated in a nonlinear fashion with both adipose and skeletal muscle MBF and CBV. There were significant linear correlations between adipose and muscle MBF (r=0.81) and CBV (r=0.66). Adipocyte cell volume on histology was 25-fold higher in 14- to 16-week db/db versus control mice.
  
  
  CONCLUSIONS
  Abnormal adipose MBF and CBV in insulin resistance can be detected by contrast-enhanced ultrasound and correlates with the degree of impairment in glucose storage. Abnormalities in adipose tissue and muscle seem to be coupled. Impaired adipose tissue perfusion is in part explained by an increase in adipocyte size without proportional vascular response.
authors: From the Knight Cardiovascular Institute (J.T.B., B.P.D., T.F., Y.Q., Y.Z., J.R.L.) and Department of Public Health and Preventative Medicine (D.P.), Oregon Health & Science University, Portland.
authors: J Todd
authors: JT
authors: Belcik
authors: From the Knight Cardiovascular Institute (J.T.B., B.P.D., T.F., Y.Q., Y.Z., J.R.L.) and Department of Public Health and Preventative Medicine (D.P.), Oregon Health & Science University, Portland.
authors: Brian P
authors: BP
authors: Davidson
authors: From the Knight Cardiovascular Institute (J.T.B., B.P.D., T.F., Y.Q., Y.Z., J.R.L.) and Department of Public Health and Preventative Medicine (D.P.), Oregon Health & Science University, Portland.
authors: Ted
authors: T
authors: Foster
authors: From the Knight Cardiovascular Institute (J.T.B., B.P.D., T.F., Y.Q., Y.Z., J.R.L.) and Department of Public Health and Preventative Medicine (D.P.), Oregon Health & Science University, Portland.
authors: Yue
authors: Y
authors: Qi
authors: From the Knight Cardiovascular Institute (J.T.B., B.P.D., T.F., Y.Q., Y.Z., J.R.L.) and Department of Public Health and Preventative Medicine (D.P.), Oregon Health & Science University, Portland.
authors: Yan
authors: Y
authors: Zhao
authors: From the Knight Cardiovascular Institute (J.T.B., B.P.D., T.F., Y.Q., Y.Z., J.R.L.) and Department of Public Health and Preventative Medicine (D.P.), Oregon Health & Science University, Portland.
authors: Dawn
authors: D
authors: Peters
authors: From the Knight Cardiovascular Institute (J.T.B., B.P.D., T.F., Y.Q., Y.Z., J.R.L.) and Department of Public Health and Preventative Medicine (D.P.), Oregon Health & Science University, Portland. linderj@ohsu.edu.
authors: Jonathan R
authors: JR
authors: Lindner
mesh_terms: D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000000981:diagnostic imaging* / Q000503:physiopathology; D000818:Animals; D006984:Hypertrophy; D007089:Image Enhancement; D007333:Insulin Resistance / Q000502:physiology*; D008815:Mice, Inbred Strains; D008833:Microcirculation / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000000981:diagnostic imaging*; D055420:Perfusion Imaging / Q000379:methods*; D014463:Ultrasonography
keywords: adipose tissue; diabetes mellitus; insulin resistance; microcirculation