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

9 Citations (Scopus)

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

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Isoxazoles
Metabolites
Gene expression
Phenotype
Gene Expression
Genes
Neuroendocrine Cells
Medical problems
Scaffolds
Regeneration
Cell Differentiation
Glucose
Molecules

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells. / Kalwat, Michael A.; Huang, Zhimin; Wichaidit, Chonlarat; McGlynn, Kathleen; Earnest, Svetlana; Savoia, Claudia; Dioum, Elhadji M.; Schneider, Jay W.; Hutchison, Michele R.; Cobb, Melanie H.

In: ACS Chemical Biology, Vol. 11, No. 4, 15.04.2016, p. 1128-1136.

Research output: Contribution to journalArticle

Kalwat, Michael A. ; Huang, Zhimin ; Wichaidit, Chonlarat ; McGlynn, Kathleen ; Earnest, Svetlana ; Savoia, Claudia ; Dioum, Elhadji M. ; Schneider, Jay W. ; Hutchison, Michele R. ; Cobb, Melanie H. / Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells. In: ACS Chemical Biology. 2016 ; Vol. 11, No. 4. pp. 1128-1136.
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