![]() (A) MS-275 treatment and its impact on palmitate-mediated pancreatic beta-cell death as assessed by MTT assay. ![]() MS275 prevents palmitate-induced cell death in cultured pancreatic beta cells. GSIS was evaluated in Figure 4 continued on next page Results are mean (± S.E) of three independent experiments *p<0.05 was determined by the analysis of variance (ANOVA) using Tukey's multiple comparison test. (E) Effect of Bafilomycin on GLP-1R-induced GSIS mediated by 1 nM liraglutide in control and MS-275-treated pancreatic beta cells. Results are mean (± S.E) of three independent experiments **p<0.01 was determined by analysis of variance (ANOVA) using Tukey's multiple comparison test. GSIS was evaluated in the presence of 16.7 mM glucose. (D) Effect of Rab5A S34N on GLP-1R-induced GSIS mediated by 1 nM liraglutide in MS-275-treated pancreatic beta cells. Results are the mean (± S.E) of three independent experiments ***p<0.001 was determined by analysis of variance (ANOVA) using Tukey's multiple comparison test comparing the effect of MS-275 on GSIS in rat islets in the presence and absence of liraglutide. (C) Effect of MS-275 on GLP-1R-induced GSIS mediated by 1 nM liraglutide in cultured rat islets. Data are mean (± S.E) of three independent experiments ***p<0.001 was determined by analysis of variance (ANOVA) using Tukey's multiple comparison test comparing the effect of MS-275 on GSIS in the presence and absence of 0.1 nM liraglutide. Insulin secretion is reported as ng/mg protein and expressed as fold over the basal secretion. (B) Effect of MS-275 on GLP-1R-mediated GSIS in BRIN-BD11 pancreatic beta cells. NES = Normalized enrichment score, FDR = False Discovery Rate. The graph depicting the profile of the running enrichment score (ES) and the position of the representative Gene Set members in the rank order list. (A) GSEA Blue-Pink O' gram of the representative genes involved in insulin secretion in control and MS-275-treated pancreatic beta cells. MS-275 stimulates GLP-1R-mediated GSIS and prevents fatty-acid-induced pancreatic beta-cell death. The online version of this article includes the following source data for figure 2: Source data 1. (G) Differential Expressed Gene (DEG) heat map by GO terms of select genes related to chromatin modification in BRIN-BD11 pancreatic beta cells (log 2 fold enrichment !2.0, p<0.05) upregulated genes in red, downregulated in blue. (F) Effect of MS-275 on H3K27 acetylation the immunoblot images are representative of three independent experiments RPL-13a immunoblot served as the loading control. The numbers on the Venn diagram indicates the number of genes shared among the pathways. All Venn Diagrams were produced with Venny 2.0.2 (). (E) Venn diagram of differentially expressed genes related to the cAMP-signaling pathway, insulin secretion pathway, and pathways involved in the energy metabolism. The graph represents the profile of the running enrichment score and positions of the Gene Set members in the rank order list. ![]() (D) GSEA Blue-Pink O' gram of the genes related to Histone modifications in the control and MS-275-treated pancreatic beta cells. Enrichment plot of the cAMP pathway in the control and MS-275 (test)-treated pancreatic beta cells depicting the profile of the running enrichment score (ES) and the position of the representative gene-set members in the rank order list. ![]() (C) GSEA BluePink O' gram of the cAMP pathway in the control and MS-275-treated pancreatic beta cells. (B) Gene ontology (GO) pathway enrichment upon MS-275 treatment in BRIN-BD11 pancreatic beta cells only significantly enriched terms shown FDR < 0.05. Red dots show upregulated while blue dots represent downregulated genes. The log 2 fold change is represented in the x-axis, whereas -log 10 of the corrective p-value is represented in the y-axis. (A) Volcano plot from hierarchical clustering of differentially expressed genes on MS-275 treatment in BRIN-BD11 pancreatic beta cells. MS-275 alters transcriptome profile in BRIN-BD11 pancreatic beta cells.
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