Figure 7. Effects of the Glucagon-like peptide-1 (GLP-1) agonist, liraglutide, on inflammatory mediators, proliferation of PSCs and activation of signaling cascades, and effects of the ERK inhibitor, U0126, on basal or liraglutide stimulated growth.

Panel A shows the RT-PCR results from 4 experiments for passages 3–5 of PSCs, comparing non-treatment (Con) with treatment with liraglutide (1000 nM) for 6 hours. Panel B shows the concentration-dependent effect of liraglutide on cell proliferation after 24 and 48 hours. Panel C shows the liraglutide-induced signaling cascade activation. Results for phospho-ERK, phospho-JNK, phospho-p38, and phospho-Akt were determined using specific phospho-antibodies. Results with IκB-α were determined using a specific IκB-α antibody. The results were determined at the indicated times with liraglutide and after a 15 min incubation with PDGF-BB. Panel D shows effects of U0126, a specific inhibitor of ERK. PSCs (passages 3–5) (2000 cells/well) were pre-incubated for 24 hours in serum free medium and then incubated for 24 hours with indicated concentrations of liraglutide alone or with U0126. U0126 was added 30 min prior to liraglutide. Growth was determined by MTS assay using coloriometric microplate reader. Results are the means ± SEM from 4 experiments.