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Nkx6.1‐mediated insulin secretion and β‐cell proliferation is dependent on upregulation of c‐Fos
Author(s) -
Ray Jason D.,
Kener Kyle B.,
Bitner Benjamin F.,
Wright Brent J.,
Ballard Matthew S.,
Barrett Emily J.,
Hill Jonathon T.,
Moss Larry G.,
Tessem Jeffery S.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12208
Subject(s) - downregulation and upregulation , secretion , cell growth , insulin , gene knockdown , microbiology and biotechnology , receptor , endocrinology , cell , medicine , chemistry , biology , gene , biochemistry
Understanding the molecular pathways that enhance β‐cell proliferation, survival, and insulin secretion may be useful to improve treatments for diabetes. Nkx6.1 induces proliferation through the Nr4a nuclear receptors, and improves insulin secretion and survival through the peptide hormone VGF . Here we demonstrate that Nkx6.1‐mediated upregulation of Nr4a1, Nr4a3, and VGF is dependent on c‐Fos expression. c‐Fos overexpression results in activation of Nkx6.1 responsive genes and increases β‐cell proliferation, insulin secretion, and cellular survival. c‐Fos knockdown impedes Nkx6.1‐mediated β‐cell proliferation and insulin secretion. These data demonstrate that c‐Fos is critical for Nkx6.1‐mediated expansion of functional β‐cell mass.