title: Evaluation of organ-specific glucose metabolism by ¹⁸F-FDG in insulin receptor substrate-1 (IRS-1) knockout mice as a model of insulin resistance.
abstract: OBJECTIVE
  Insulin resistance (IR) is a physiological condition in which the body produces insulin but does not result in a sufficient biological effect. Insulin resistance is usually asymptomatic but is associated with health problems and is a factor in the metabolic syndrome. The aim of the present study is to clarify organ-specific insulin resistance in normal daily conditions using [(18)F]-2-fluoro-2-deoxy-D: -glucose ([(18)F]-FDG).
  
  
  METHODS
  The biodistribution of [(18)F]-FDG was examined in insulin receptor substrate-1 (IRS-1) knockout mice, an animal model of skeletal muscle insulin resistance, and C57BL/6J (wild-type) mice with and without insulin loading. Mice received 0.5 MBq of [(18)F]-FDG injected into the tail vein, immediately followed by nothing (control cohorts) or an intraperitoneal injection of 1.5 mU/g body weight of human insulin as an insulin loading test. Blood glucose concentrations for all of the experimental animals were assessed at 0, 20, 40, and 60 min post-injection. The mice were subsequently killed, and tissue was collected for evaluation of [(18)F]-FDG biodistribution. The radioactivity of each organ was measured using a gamma counter.
  
  
  RESULTS
  In the absence of insulin, the blood glucose concentrations of wild-type mice (132 ± 26 mg/dl) and IRS-1 knockout mice (134 ± 18 mg/dl) were not significantly different. Blood glucose concentrations decreased following insulin administration, with lower concentrations in wild-type mice than in knockout mice at 20, 40, and 60 min. A statistically significant difference in [(18)F]-FDG uptake between wild-type mice and IRS-1 knockout mice was confirmed in the heart, abdominal muscle, and femoral muscle. With insulin loading, [(18)F]-FDG uptake in the heart, back muscle, and abdominal muscle was significantly increased compared to without insulin loading in both wild-type mice and knockout mice.
  
  
  CONCLUSIONS
  Our results showed that IR significantly affected [(18)F]-FDG uptake in the heart in normal daily conditions. IR was associated with decreased [(18)F]-FDG uptake in the heart and was readily observed in the absence of insulin loading. [(18)F]-FDG-positron emission tomography (PET) could be a useful tool for evaluating insulin resistance in images by investigating tissue-specific differences in [(18)F]-FDG uptake.
authors.affiliation: Department of Radiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.forename: Akinobu
authors.initials: A
authors.lastname: Nakamura
authors.forename: Ryogo
authors.initials: R
authors.lastname: Minamimoto
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shinoda
authors.forename: Ukihide
authors.initials: U
authors.lastname: Tateishi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Goto
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Tomio
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18 / Q000097:blood / Q000493:pharmacokinetics*; D055786:Gene Knockout Techniques; D007267:Injections; D055504:Insulin Receptor Substrate Proteins / Q000172:deficiency* / Q000235:genetics*; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D049268:Positron-Emission Tomography; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D019788:Fluorodeoxyglucose F18