Fig 2: The expressions of GLP1R and PKA in EC cells. (A) The expression of GLP1R in hEEC, Ishikawa cells and RL95-2 cells was quantified by qRT-PCR, with ß-actin serving as the internal reference. (B and C) GLP1R expression in Ishikawa and RL95-2 cells of the Con, Vector and OE-GLP1R groups was also detected by qRT-PCR, with ß-actin serving as the internal reference. (D and E) QRT-PCR was used to determine the expression of PKA in the Con, si-NC and si-PKA groups, with ß-actin serving as the internal reference. All experiments were repeated three times to obtain average values. The data from three independent experiments were presented as the mean ± SD; ***p < 0.001 versus hEEC; ^^^ p < 0.001 versus Vector; ### p < 0.001 versus si-NC. Con, control; EC, endometrial carcinoma; GLP1R, glucagon-like peptide-1 receptor; hEEC, human endometrial epithelial cell; OE-GLP1R, GLP1R overexpression; PKA, protein kinase A; qRT-PCR, quantitative reverse transcription polymerase chain reaction; SD, standard deviation; si-NC, siRNA negative control; si-PKA, small interference RNA targeting PKA.

Fig 3: Summary diagram of the relationship among GLP-1, CML and PPAR in cells apoptosis. CML could induce the apoptosis of PC12 cells. GLP-1 could induce the expression of PPAR-? by binding to GLP-1R. And then, PPAR-? could attenuate the neuronal apoptosis. Additionally, PPAR-? may promote the expression of GLP-1R by the interaction between PPAR-? and the promoter sequence of GLP-1R.

Fig 4: Levels of apoptosis were elevated in hippocampus of diabetic rats. “a” in (A) showed elevated CML levels in hippocampus of diabetic rats, compared with control rats (P<0.05). “a” in (B) showed decreased GLP-1 levels in hippocampus of diabetic rats, compared with control rats (P<0.05). Results in (C) showed increased apoptosis in hippocampus of diabetic rats, compared with control rats. Results in (D) showed down-regulated PPAR-? and GLP-1R in hippocampus of diabetic rats, compared with control rats. (E) Showed the western blotting results of bcl2, bax, GLP-1R and PPAR-?. “a” of (F) showed down-regulated bcl2, GLP-1R and PPAR-? levels and up-regulated bax levels in hippocampus of diabetic rats, compared with control rats (all P<0.05). Data are represented as mean ± SD; n=4 per group for results of ELISA. n=3 per group for results of western blotting.

Fig 5: The sketch map demonstrated the mechanism involved in liraglutide alleviated hepatic steatosis and liver injury. GLP-1 agonist liraglutide could directly act on hepatic GLP-1R to stimulate the expression of PPARa through activating the PKA-AMPK signaling pathway. PPARa could stimulate the ß-oxidation to relieve hepatic steatosis through stimulating the expression of CPT1a and decreasing that of ACC. Meanwhile, PPARa could also decrease the intracelluar ROS level to alleviate the liver injury. On the other hand, insulin could suppress the expression of GLP-1R to inhibit its downstream signaling, while the administration of GLP-1 could recover the insulin aggravated hepatic steatosis.