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 language | English (US) |
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Pages (from-to) | 1128-1136 |
Number of pages | 9 |
Journal | ACS chemical biology |
Volume | 11 |
Issue number | 4 |
DOIs | |
State | Published - Apr 15 2016 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine