Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β‑Cells Michael A. Kalwat Zhimin Huang Chonlarat Wichaidit Kathleen McGlynn Svetlana Earnest Claudia Savoia Elhadji M. Dioum Jay W. Schneider Michele R. Hutchison Melanie H. Cobb 10.1021/acschembio.5b00993.s006 https://acs.figshare.com/articles/dataset/Isoxazole_Alters_Metabolites_and_Gene_Expression_Decreasing_Proliferation_and_Promoting_a_Neuroendocrine_Phenotype_in_Cells/2081395 Novel strategies are needed to modulate β-cell differentiation and function as potential β-cell replacement or restorative therapies for diabetes. We previously demonstrated that small molecules based on the isoxazole scaffold drive neuroendocrine phenotypes. The nature of the effects of isoxazole compounds on β-cells was incompletely defined. We find that isoxazole induces genes that support neuroendocrine and β-cell phenotypes and suppresses genes important for proliferation. Isoxazole alters β-cell metabolites and protects glucose-responsive signaling pathways under lipotoxic conditions. Finally, we show that isoxazole improves glycemia in a mouse model of β-cell regeneration. Isoxazole is a prime candidate to alter cell fate in different contexts. 2016-02-01 00:00:00 mouse model cell fate isoxazole scaffold drive neuroendocrine phenotypes Gene Expression Neuroendocrine Phenotype isoxazole compounds support neuroendocrine Isoxazole Alters Metabolites lipotoxic conditions