Fig. 2
From: Antidiabetic and cardiovascular beneficial effects of a liver-localized mitochondrial uncoupler
Antidiabetic effects of OPC-163493 in a wide variety of animal models. a Effect of repetitive oral dosing with OPC-163493 (BID) on HbA1c changes from baseline in male ZDF Rats. OPC treatments were performed on rats aged between 11 and 17 weeks. Data represent mean ± SE (n = 16). Significant efficacy was found in the 2, 4, and 10 mg kg−1 day−1 OPC-163493-treated groups (∗P < 0.05, ∗∗P < 0.01, OPC vs. vehicle group using Williams’ test with two-way ANOVA). b Effect of OPC-163493 dosing with mixed chow on HbA1c values in male Akita mice. OPC treatments were performed on mice aged between 6 and 12 weeks. Data represent mean ± SE (n = 12). Significant efficacy was found in the 0.01 and 0.02% OPC-163493-treated groups (∗∗P < 0.01, OPC vs. control chow group using a two-tailed Williams’ test). c Effect of OPC-163493 repetitive oral dosing (BID) on HbA1c changes from baseline in old male ZDF rats having extreme insulin resistance. OPC treatments were performed on rats aged between 27 and 33 weeks. Data represent mean ± SE (n = 6). Significant efficacy was found in the 6 and 10 mg kg−1 day−1 OPC-163493-treated groups on day 28, and in the 10 mg kg−1 day−1 OPC-163493-treated group on day 43 (∗P < 0.05, ∗∗P < 0.01, OPC vs. vehicle group using a two-tailed Williams’ test). d Long-term effect of OPC-163493 dosing with mixed chow on HbA1c values in male OLETF rats. Twenty-week treatments were carried out between the age of 27 and 47 weeks. LETO (Long-Evans Tokushima Otsuka) rats were used as normoglycemic control rats. Data represent mean ± SE (n = 14) except for LETO (n = 6). Significant efficacy was found in the 0.02 and 0.06% OPC-mixed chow-treated groups using a mixed model for repeated measures (MMRM) method followed by Dunnett’s test (OPC vs. control chow group, P < 0.01). Black diamond, control chow; open triangle, 0.01% chow; open square, 0.02% chow; open circle, 0.06% chow; cross, LETO rats with control chow. e Long-term effect of OPC-163493 on oxidative stress markers in OLETF rats. Data represent mean ± SE (n = 14) except for LETO (n = 6). Significant improvements were found in the 0.02 and 0.06% for 8-OHdG, and 0.01, 0.02, and 0.06% OPC-mixed chow-treated groups for 8-isoprostane using a two-tailed Williams’ test (OPC vs. control chow group, ∗P < 0.05, ∗∗P < 0.01). A significant difference was also observed for 8-isoprostane between the LETO rat group and the OLETF rat (control chow) group using an unpaired t test (##P < 0.01). f Effect of OPC-163493 dosing with mixed chow on HbA1c in male ZDF(M) rats. Each value represents the mean ± SE (n = 8). A significant difference was found (∗∗P < 0.01, unpaired t test). g Effects of OPC-163493 on spontaneous locomotor activity in ZDF(M) rats. Measurements were carried out before (baseline) and after 4 weeks of treatment (day 28). Each value represents the mean ± SE (n = 8). No significant difference was found (unpaired t test). Black bar, control; gray bar, OPC-163493. h Effects of OPC-163493 on energy expenditure in ZDF(M) rats. Each value represents the mean ± SE (n = 8). No significant difference was found (unpaired t test). Black bar, control; gray bar, OPC-163493. i Effects of OPC-163493 on respiratory exchange ratio (RER) in ZDF(M) rats. Each value represents the mean ± SE (n = 8). A significant difference was found at baseline in the light period (∗P < 0.05, unpaired t test); however, no significant difference was found after treatment. Black bar, control; gray bar, OPC-163493
