Insulin secretion from pancreatic β-cells is essential for glucose homeostasis. An insufficient response to the demand for insulin results in diabetes. We previously showed that β-cell-specific deletion of Zfp148 (β-Zfp148KO) improves glucose tolerance and insulin secretion in mice. These RNA sequencing data show pathways altered in the β-Zfp148KO consistent with altered PEP cycling and improved insulin secretion responses. Overall design: Details of generating the β-Zfp148KO and their control littermates is provided by Keller et al. JCI 2019 (https://doi.org/10.1172/JCI129143). 5 female littermate control (floxed Zfp148), 6 female β-Zfp148KO, 5 male control, and 4 male β-Zfp148KO mice were placed on a high-fat, high-sucrose diet (TD.08811) for 20 weeks. They were then sacrificed. RNA extracts and cDNA were prepared from whole islets harvested from these mice. RNA sequencing was performed by the UW-Madison Biotechnology Center. Processed sequencing data were analyzed by EBSeq (for EBSeq method, see Leng et al. https://doi.org/10.1093/bioinformatics/btt087).