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Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells.

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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Kalwat MA,Huang Z,Wichaidit C,McGlynn K,Earnest S,Savoia C,Dioum EM,Schneider JW,Hutchison MR,Cobb MH

doi

10.1021/acschembio.5b00993

subject

Has Abstract

pub_date

2016-04-15 00:00:00

pages

1128-36

issue

4

eissn

1554-8929

issn

1554-8937

journal_volume

11

pub_type

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