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Determining the Role of CEBP/α in Functional β‐cell Mass
Author(s) -
Kener Kyle B,
Ray Jason D.,
Ballard Matthew,
Utsch Will,
Tessem Jeffery Sivert
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.715.1
Subject(s) - cell growth , cell , downregulation and upregulation , microbiology and biotechnology , apoptosis , cancer research , in vivo , biology , chemistry , gene , biochemistry , genetics
Type 1 and type 2 diabetes both result in decreased functional β‐cell mass. Increasing functional β‐cell mass could be used as a cure for diabetes, either through the ex vivo expansion of β‐cells for transplantation or through in vivo expansion of endogenous β‐cells. We have shown that Nkx6.1 is necessary and sufficient to increase functional β‐cell mass by increasing proliferation, enhancing β‐cell function, and improving β‐cell survival. Furthermore, we have shown that c‐Fos is a critical early‐activated Nkx6.1 target gene that is essential to implement this molecular pathway. Here we demonstrate that CEBP/α is necessary for Nkx6.1 mediated upregulation of c‐Fos. We show that Nkx6.1 induces expression of CEBP/α, and that CEBP/α induces expression of c‐Fos. We show that CEBP/α is sufficient to induce β‐cell proliferation. We show that overexpression of CEBP/α protects β‐cells from apoptotic stimuli. We demonstrate the effect of CEBP/α overexpression on glucose stimulated insulin secretion. These data support the hypothesis that CEBP/α is part of the Nkx6.1 pathway for maintaining and increasing functional β‐cell mass and suggest that CEBP/α could be used as a potential target for enhancing functional β‐cell mass. Support or Funding Information BYU MEG Grant to JST, BYU ORCA Grant to JDR and KBK