Fig 2: Nondiabetic plasma-treated SVFs increase Akt activation and attenuate glucose intolerance in Leprdb/db mice. A Leprdb/db SVFs were treated with plasma from Lepr+/+ mice. Increased numbers (1 × 107 and 2 × 107) of Lepr+/+ plasma-treated SVFs were injected into the inguinal WAT of Leprdb/db mice. Lepr+/+ and Leprdb/db mice treated with PBS were served as controls. One week after injection, mice were treated with vehicle or insulin 1.25 mIU/g body weight for 20 min. Mice were then killed and SVFs were harvested followed by western blot analysis for pAkt, Akt, pERK, and ERK expression. B The ratios of pAkt/Akt and pERK/ERK were calculated. C After 15 h fasting, Lepr+/+ mice treated with PBS, Leprdb/db mice treated with PBS, and Leprdb/db mice injected with Lepr+/+ plasma-treated SVFs were administered with glucose. The blood glucose level was measured before and every 15 min up to 2 h after glucose administration by using a glucose meter. N = 4/group. *p < 0.05; **p < 0.01; ***p < 0.001 compared to Lepr+/+ mice. #p < 0.05; ##p < 0.01 compared to Leprdb/db mice

Fig 3: Effects of CGA on Nrf2 nuclear translocation and PI3K/Akt phosphorylation in MC3T3-E1 cells(A) and (C) Cells were treated with CGA (100 µM) for indicated time points (0, 1, 3, 6 and 12 h). (B) and (D) Cells were treated with indicated concentrations (0, 25, 50 and 100 µM) of CGA for 3 h. (A) and (B) The nuclear and cytosolic levels of Nrf2 were determined by western blot analysis. PCNA was used as nuclear loading control. (C) and (D) Cell lysates were subjected to western blot analysis with anti-Akt or p-Akt antibodies. ß-actin was used as loading control. *p < 0.01 indicates the significant difference compared with control group.

Fig 4: Caudatin disturbs the VEGF-VEGFR2-AKT signal axis. (A) Caudatin suppressed the expression of VEGF-VEGFR2-AKT signal axis. (B) AKT inhibitor (LY294002) enhanced caudatin-induced growth inhibition against HUVECs. Cells were pre-treated with 10 µM LY294002 for 2 h before caudatin treatment. Cell viability was determined by MTT assay. Different letters on bars are statistically different at P<0.05 level when compared between any two groups. HUVEC, human umbilical vein endothelial cells; VEGF, vascular endothelial growth factor; AKT, protein kinase B; MTT, 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide.

Fig 5: Chlamydia trachomatis hijacks Akt/AS160/Rab14 cascade to acquire Golgi-derived sphingolipids. Ct phosphorylates and recruits pAkt to the inclusion membrane by one or more cognate effectors (CT effector). Upon Akt activation, AS160 is inactivated by phosphorylation and it is detached from the inclusion membrane. Hindered AS160 GAP-activity enables Rab14 to remain in its GTP-bound membrane-associated active form. This, in turn, favors the arrival to chlamydial inclusions of sphingolipids synthesized at the Golgi apparatus through a Rab14-controlled vesicular transport.