title: Influence of dietary state and insulin on myocardial, skeletal muscle and brain [F]-fluorodeoxyglucose kinetics in mice.
abstract: BACKGROUND
  We evaluated the effect of insulin stimulation and dietary changes on myocardial, skeletal muscle and brain [(18)F]-fluorodeoxyglucose (FDG) kinetics and uptake in vivo in intact mice.
  
  
  METHODS
  Mice were anesthetized with isoflurane and imaged under different conditions: non-fasted (n = 7; "controls"), non-fasted with insulin (2 IU/kg body weight) injected subcutaneously immediately prior to FDG (n = 6), fasted (n = 5), and fasted with insulin injection (n = 5). A 60-min small-animal PET with serial blood sampling and kinetic modeling was performed.
  
  
  RESULTS
  We found comparable FDG standardized uptake values (SUVs) in myocardium in the non-fasted controls and non-fasted-insulin injected group (SUV 45-60 min, 9.58 ± 1.62 vs. 9.98 ± 2.44; p = 0.74), a lower myocardial SUV was noted in the fasted group (3.48 ± 1.73; p < 0.001). In contrast, the FDG uptake rate constant (K(i)) for myocardium increased significantly by 47% in non-fasted mice by insulin (13.4 ± 3.9 ml/min/100 g vs. 19.8 ± 3.3 ml/min/100 g; p = 0.030); in fasted mice, a lower myocardial K(i) as compared to controls was observed (3.3 ± 1.9 ml/min/100 g; p < 0.001). Skeletal muscle SUVs and K(i) values were increased by insulin independent of dietary state, whereas in the brain, those parameters were not influenced by fasting or administration of insulin. Fasting led to a reduction in glucose metabolic rate in the myocardium (19.41 ± 5.39 vs. 3.26 ± 1.97 mg/min/100 g; p < 0.001), the skeletal muscle (1.06 ± 0.34 vs. 0.34 ± 0.08 mg/min/100 g; p = 0.001) but not the brain (3.21 ± 0.53 vs. 2.85 ±0.25 mg/min/100 g; p = 0.19).
  
  
  CONCLUSIONS
  Changes in organ SUVs, uptake rate constants and metabolic rates induced by fasting and insulin administration as observed in intact mice by small-animal PET imaging are consistent with those observed in isolated heart/muscle preparations and, more importantly, in vivo studies in larger animals and in humans. When assessing the effect of insulin on the myocardial glucose metabolism of non-fasted mice, it is not sufficient to just calculate the SUV - dynamic imaging with kinetic modeling is necessary.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kreissl
authors.forename: David B
authors.initials: DB
authors.lastname: Stout
authors.forename: Koon-Pong
authors.initials: KP
authors.lastname: Wong
authors.forename: Hsiao-Ming
authors.initials: HM
authors.lastname: Wu
authors.forename: Evren
authors.initials: E
authors.lastname: Caglayan
authors.forename: Waldemar
authors.initials: W
authors.lastname: Ladno
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: John O
authors.initials: JO
authors.lastname: Prior
authors.forename: Christoph
authors.initials: C
authors.lastname: Reiners
authors.forename: Sung-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: Heinrich R
authors.initials: HR
authors.lastname: Schelbert