Effect of 7 days of SGLT2-I treatment on hepatic insulin sensitivity. ZDF rats were given (from 9 weeks of age) vehicle (ZDF-V7) or an SGLT2-I (ZDF-CA7) daily for 7 days before a clamp study. Animals were fasted for 6 h before each clamp study, and livers were collected at the end of the test period (a basal [no clamp] period or a hyperinsulinemic-hyperglycemic [HI-HG] clamp) (Fig. 2). A: Representative images from Western blotting of protein extracts prepared from livers that were probed with antibodies for the detection of total Akt, p-AktThr308, p-AktSer473, and β-actin and measurement of the relative abundance of p-AktThr308 (B), p-AktSer473 (C), Akt (D), and GK (E) and PEPCK (F) mRNA. Quantitative results were normalized to the average basal value of ZDF-V7 for relative abundance. Values are the mean ± SEM of data from six animals in each group. *Significant difference from the corresponding values of the ZDF-V7 group within each treatment (P < 0.05); †significant difference from the basal values of the identical group (P < 0.05).