Reductions in β cell number and/or function underlie all forms of diabetes; thus, understanding the mechanisms that shape β cell health may hold therapeutic utility. While much focus to date has centered on understanding transcriptional control of β cell function and survival, these processes are also critically regulated at the post-transcriptional level. In particular, RNA binding proteins (RBPs) are master regulators of mRNA metabolism, yet an understanding of the influence of these factors in shaping β cell homeostasis remains relatively limited. In the first part of this dissertation, we demonstrate roles for the RBP PCBP2 in directing β cell function under basal and sustained hyperglycemic conditions. We find that incubating murine islets with high glucose upregulates PCBP2 through increased stability while also augmenting stimulus-coupled insulin secretion. shRNA-mediated depletion of Pcbp2 in β cells revealed a requirement for this factor in the adaptive insulin secretory response. Transcriptomic analysis of Pcbp2 null β cells under basal and high glucose conditions uncovered impacts on mRNAs implicated in maintaining and adapting the insulin secretory pathway. Mechanistic studies identified that PCBP2 regulates its mRNAs in part through binding and stability. Functional and ultrastructure analysis revealed that Pcbp2 null β cells harbor defects in intracellular calcium flux, insulin granule ultrastructure and docking, and the amplification pathway of insulin secretion. We further find that PCBP2 is glucose-induced in human islets while downregulated in islets from human subjects with type 2 diabetes. In the second part of this dissertation, we examine the relationship of PCBP2 and its sister-isoform PCBP1 in the β cell, uncovering shared roles for these factors in directing a program of translational machinery mRNAs critical for promoting β cell translation and survival. Co-deleting Pcbp1 and Pcbp2 in β cells in mice resulted in overt diabetes due to compromised β cell viability. Single-cell RNA sequencing paired with motif, mRNA-protein interaction, and mRNA stability studies revealed that the PCBPs targeted translational machinery mRNAs necessary for maintaining global mRNA translation in part through binding and transcript stabilization. Altogether, these studies establish the PCBPs as key post-transcriptional determinants of β cell homeostasis.