Effect of linagliptin on insulin sensitivity determined by euglycemic–hyperinsulinemic clamps in diet-induced obesity (DIO) mice.

<p>C57BL/6 mice were fed a high-fat diet (HFD) or chow diet for 3 months followed by treatment with linagliptin (3 mg/kg/day or 30 mg/kg/day) or placebo. Four weeks after treatment initiation, euglycemic–hyperinsulinemic clamps were performed to measure glucose disposal rate (GDR) (A), dynamic of blood glucose concentrations (B), and GDR and hepatic glucose production (HGP) during the steady-state period of the euglycemic–hyperinsulinemic clamp (C and D). (E–H) Tissue specific uptake of 2-deoxy-<i>d</i>-[1-¹⁴C]glucose into gastrocnemius skeletal muscle (E), heart muscle (F), perigonadal white adipose tissue (WAT) (G) and kidney (H). Blood glucose levels were determined every 10 minutes (B-Glucose Analyzer; HemoCue AB, Ängelholm, Sweden). Values are given as mean ± SD. ***<i>P</i><0.001 compared with DIO vehicle-treated group.