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

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1128-1136
Number of pages9
JournalACS Chemical Biology
Volume11
Issue number4
DOIs
StatePublished - Apr 15 2016

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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    Kalwat, M. A., Huang, Z., Wichaidit, C., McGlynn, K., Earnest, S., Savoia, C., Dioum, E. M., Schneider, J. W., Hutchison, M. R., & Cobb, M. H. (2016). Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells. ACS Chemical Biology, 11(4), 1128-1136. https://doi.org/10.1021/acschembio.5b00993