A human beta-cell line, RNAKT-15, was recently established from human pancreatic islets, whereby its differentiation into islet-like beta-cells (islet-like RNAKT-15) increased its expression of insulin 2-fold compared with RNAKT-15 cells. To characterize the differentiation of RNAKT-15 cells into islet-like RNAKT-15, microarray and quantitative proteomics were performed. Our analysis of differential proteomic and mRNA expression has resulted in a greater understanding of the molecular functions that are involved in beta-cell differentiation and insulin synthesis and release.