GSK3α inhibitor improves insulin sensitivity and glucose tolerance in mice fed on HFHSD. (A) Schematic of GSK3α pharmacological inhibition in mice with HFHSD and the time points for indicated experiments. (B) The body weight of mice treated with vehicle or GSK3α inhibitor (BRD0705; n = 15 mice per group). (C and D) Glucose and insulin tolerance tests after vehicle or BRD0705 were delivered for 34–35 wk. The blood glucose levels were measured at indicated times after peritoneal injection of glucose (C) or insulin (D; n = 15 mice for vehicle group, n = 14 mice for BRD0705 group). (E–H) Effect of BRD0705 on Dyn2 phosphorylation and insulin signaling pathway. Soleus muscle from vehicle- or BRD0705-treated mice were collected 30 min after insulin injection (2 IU/kg), lysed, and detected by Western blotting with indicated antibodies. The ratio of p-Dyn2^S848 (E), Akt^S473 (F), GSK3α^S21 (G), and GSK3β^S9 (H) normalized to total protein was quantified and shown (n = 15 tissue lysates for vehicle group, n = 10 tissue lysates for BRD0705 group). Data are shown as average ± SEM and analyzed with Student’s t test (two-tailed, unpaired, B–D) or one-way ANOVA (E–H). *P < 0.05; **P < 0.01; ***P < 0.001. Molecular weight is in kD. Source data are available for this figure: SourceData F8.