Figure 3.

INS^Δ123/Δ123SC-islets exhibit reduced IR signaling. A) Principal component analysis (PCA) of INS^Cherry/WT and INS^Δ123/Δ123 SC-islets at S5.7. B) Volcano plot showing the log2 fold changes of proteins with respect to the log of FDR (0.1). C) Differentially upregulated and downregulated proteins in INS^Δ123/Δ123 vs INS^Cherry/WT SC-islets. D) Selected terms from the pathway analysis of downregulated and upregulated proteins in INS^Δ123/Δ123 SC-islets. E-H) Heat maps of significantly downregulated proteins associated with insulin signaling, spliceosome, protein folding and vesicle trafficking in INS^Δ123/Δ123 compared INS^Cherry/WT SC-islets s. I) Heat map of significantly upregulated proteins associated with intracellular signaling proteins in INS^Δ123/Δ123 compared INS^Cherry/WT SC-islets. J) Representative Western blot picture showing the phosphorylation of IR, IGF1R, and AKT from WT, INS^Cherry/WT and INS^Δ123/Δ123 SC-islets at S6.21 treated with 20 mM glucose in the absence and presence of 100 nM exogenous insulin. K-N) Quantifications of phosphorylated IR-IGF1R and the total IR in SC-islets treated with 20 mM glucose in the absence (No insulin) and presence (+insulin) of exogenous insulin. O, P) Quantifications of phosphorylated AKT in SC-islets treated with 20 mM glucose in the absence (No insulin) and presence (+insulin) of exogenous insulin. Data are normalized to WT (K–P). All statistics have been done using one-way ANOVA multiple comparisons test. Data are represented as mean ± SD.