TY - JOUR T1 - Insulin Stimulates Liver Glucose Uptake in Humans: An <sup>18</sup>F-FDG PET Study JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 682 LP - 689 VL - 44 IS - 5 AU - Patricia Iozzo AU - Fabian Geisler AU - Vesa Oikonen AU - Maija Mäki AU - Teemu Takala AU - Olof Solin AU - Ele Ferrannini AU - Juhani Knuuti AU - Pirjo Nuutila Y1 - 2003/05/01 UR - http://jnm.snmjournals.org/content/44/5/682.abstract N2 - The liver is vital for the regulation of glucose metabolism, but inaccessibility of the organ for direct assessments has limited the study of its metabolic role in vivo. Methods: The effect of insulin and insulin sensitivity (IS) on hepatic glucose uptake was investigated using PET, 18F-FDG, and graphical analysis and 3-compartment modeling in humans. We studied 16 healthy sedentary men (normal IS), 8 athletes (high IS), and 7 patients with coronary artery disease (low IS) either during fasting (n = 14) or during euglycemic hyperinsulinemia (n = 24). Results: Whole-body insulin-mediated glucose uptake was 35 ± 7 μmol/min/kg for normal-IS subjects, 65 ± 8 μmol/min/kg for high-IS subjects (P &lt; 0.05 vs. normal IS), and 24 ± 3 μmol/min/kg for low-IS subjects (P &lt; 0.05 vs. normal IS and high IS). Hyperinsulinemia enhanced hepatic glucose influx (2.3 ± 0.9 vs. 1.5 ± 0.7 μmol·min−1·100 mL−1, P &lt; 0.05) and phosphorylation rates (0.55 ± 0.24 vs. 0.36 ± 0.19 min−1·10−2, P &lt; 0.05) similarly in insulin-sensitive and -resistant subjects. During hyperinsulinemia, however, the glucose phosphorylation-to-dephosphorylation ratio was significantly lower in the low-IS group than in normal-IS subjects (P &lt; 0.05) or high-IS subjects (P &lt; 0.01); correspondingly, whole-body insulin-mediated glucose disposal was directly related to this ratio (r = 0.45; P &lt; 0.05). Furthermore, glucose influx rates were inversely correlated with fasting plasma free fatty acids (P &lt; 0.05). Both compartmental modeling and the graphical approach accurately described the data, though the latter yielded slightly lower estimates of glucose influx rates during fasting. Conclusion: Our study provided evidence that physiologic hyperinsulinemia enhances hepatic glucose uptake and that IS is related to the glucose phosphorylation-to-dephosphorylation balance in the liver. Graphical analysis and modeling proved to be applicable and complementary tools for the investigation of glucose metabolism in the liver. ER -