Evaluation of organ-specific glucose metabolism by 18F-FDG in insulin receptor substrate-1 (IRS-1) knockout mice as a model of insulin resistance

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 [18F]-2-fluoro-2- deoxy-D-glucose ([18F]-FDG). Methods The biodistribution of [18F]-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 [18F]-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 [18F]-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 [18F]-FDG uptake between wild-type mice and IRS-1 knockout mice was confirmed in the heart, abdominal muscle, and femoral muscle. With insulin loading, [18F]-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. Conclusion Our results showed that IR significantly affected [18F]-FDG uptake in the heart in normal daily conditions. IR was associated with decreased [18F]-FDG uptake in the heart and was readily observed in the absence of insulin loading. [18F]-FDG-positron emission tomography (PET) could be a useful tool for evaluating insulin resistance in images by investigating tissue-specific differences in [18F]-FDG uptake.