Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells
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- 作者：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
- 刊名：ACS Chemical Biology
- 出版年：2016
- 出版时间：April 15, 2016
- 年：2016
- 卷：11
- 期：4
- 页码：1128-1136
- 全文大小：641K
- 年卷期：0
- ISSN：1554-8937
文摘
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.