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Relationship between total body weight and lean body weight. DEXA scans were used to determine the lean body weight of mice fed a (A) normal diet or (B) a high�\fat diet for 1, 3, 8, 12, or 16 weeks. Lean body weight was expressed as a function ... Figure 2. Total glucose load given during the IVGTT in each of the dosing regimens. d�\glucose was injected into the tail vein at a dose of 0.35 g/kg total body weight, lean body weight, or a fixed body weight based on the average of all experimental mice ... Figure 3. Intravenous glucose tolerance tests. Baseline blood samples were taken and 0.35 g/kg d�\glucose Alpelisib research buy was injected into the tail vein. Blood samples were taken at 1, 5, 10, 20, 30, and 50 min thereafter and plasma was analyzed for glucose (A�CC) ... Mice were also injected with a fixed glucose dose irrespective of the weight of the individual animal. This dose was 0.35 g/mean kg body weight based on an average body weight of all animals irrespective of diet (11 mg/mouse). The fixed�\dose glucose injection resulted in hyperglycemia in the HFD fed mice with commensurate hyperinsulinemia (Fig. ?(Fig.3C3C and F) similar to HFD fed mice dosed based on total body weight. Using the glucose elimination rate constant KG derived from the IVGTT data, only the fixed glucose dose strategy detected the impairment of glucose elimination induced by HFD feeding (Fig. ?(Fig.4A).4A). Although all of the dosing strategies showed trends toward higher acute insulin responses (AIR) in the HFD mice, only the total body weight�Cbased glucose dosing regimen resulted in statistically Bosutinib research buy significant increases in AIR (Fig. ?(Fig.44B). Figure 4. Minimal model parameters derived from IVGTT data. Glucose and insulin concentrations during the IVGTT were used to calculate the (A) glucose elimination constant KG, (B) acute insulin response (AIR), (C) insulin sensitivity index SI, and (D) ... Using the minimal model analysis of IVGTT data, we determined insulin sensitivity (SI) in the mice with each of the glucose dosing regimens. Each of the glucose dosing regimens demonstrated significant decreases in insulin sensitivity in Dabigatran mice fed a HFD (Fig. ?(Fig.4C).4C). As regards the disposition index (the product of SI and AIR), only the fixed glucose dose regimen was able to identify the expected impairment resulting from HFD feeding (Fig. ?(Fig.4D).4D). �©\cell function was significantly improved in HFD fed mice when dosed according to total body weight, but not according to dosing by lean body mass or fixed glucose dose (Fig. ?(Fig.55). Figure 5. Evaluation of �©\cell function. The insulinogenic index was calculated from the IVGTT data as peak insulin divided by peak glucose. N =13�C14 per group. *P