Fig 2: MDK‐SDC4 interaction damages beta cell function by inhibiting Ras signaling pathway. A) Expression of potential MDK receptors in human islets from T2DM and T3cDM patients. B) Knockdown efficiency of NCL, NOTCH2 and SDC4 in beta‐TC‐6 cells was determined by RT‐qPCR. C) The protein levels of insulin in beta‐TC‐6 cells. D) The interaction between MDK and SDC4 was detected by the immunofluorescence assay in beta‐TC‐6 cells. E) The relative mRNA levels of INS1 and INS2 in the indicated beta cells treated with rmMDK. F) Low and high glucose‐stimulated insulin secretion levels in the indicated beta cells treated with rmMDK. G) The protein levels of insulin in the indicated cells treated with control medium and conditioned mediums from PDAC cells. H) The relative mRNA levels of INS1 and INS2 in the indicated cells treated with conditioned mediums from CFPAC‐1 cells (left panel) and PANC1 cells (right panel). I) Low and high glucose‐stimulated insulin secretion levels in the indicated beta cells treated with conditioned mediums from CFPAC‐1 cells. J) Heatmap showing differentially expressed genes between rmMDK‐treated and control beta‐TC‐6 cells. K) Bar plot displaying top 30 enriched signaling pathways in the GSEA analysis. L) GSEA plot of Ras signaling pathway. M) Western blotting analysis of the Ras/Raf/MEK/ERK signaling pathway in beta‐TC‐6 cells treated with rmMDK. N) Western blotting analysis of the Ras/Raf/MEK/ERK signaling pathway in the indicated beta‐TC‐6 cells treated with rmMDK. ns, not significant; * p < 0.05; ** p < 0.01; and *** p < 0.001, means ± SD was shown. Student's t‐test analysis was used for comparison between two groups.