cb5b00993_si_006.xlsx (132.72 kB)
Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β‑Cells
dataset
posted on 2016-02-01, 00:00 authored by Michael
A. Kalwat, Zhimin Huang, Chonlarat Wichaidit, Kathleen McGlynn, Svetlana Earnest, Claudia Savoia, Elhadji
M. Dioum, Jay W. Schneider, Michele R. Hutchison, Melanie H. CobbNovel 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.