title: 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.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kalwat
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Huang
authors.forename: Chonlarat
authors.initials: C
authors.lastname: Wichaidit
authors.forename: Kathleen
authors.initials: K
authors.lastname: McGlynn
authors.forename: Svetlana
authors.initials: S
authors.lastname: Earnest
authors.affiliation: Nestle Institute of Health Sciences , Lausanne, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Savoia
authors.affiliation: Nestle Institute of Health Sciences , Lausanne, Switzerland.
authors.forename: Elhadji M
authors.initials: EM
authors.lastname: Dioum
authors.forename: Jay W
authors.initials: JW
authors.lastname: Schneider
authors.forename: Michele R
authors.initials: MR
authors.lastname: Hutchison
authors.forename: Melanie H
authors.initials: MH
authors.lastname: Cobb
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D007555:Isoxazoles / Q000494:pharmacology*
chemical_list: D007555:Isoxazoles
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