Determining the Role of CEBP/α in Functional β‐cell Mass
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 nec...
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crwiley:10.1096/fasebj.31.1_supplement.715.1 2024-06-02T08:12:48+00:00 Determining the Role of CEBP/α in Functional β‐cell Mass Kener, Kyle B Ray, Jason D. Ballard, Matthew Utsch, Will Tessem, Jeffery Sivert 2017 http://dx.doi.org/10.1096/fasebj.31.1_supplement.715.1 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor The FASEB Journal volume 31, issue S1 ISSN 0892-6638 1530-6860 journal-article 2017 crwiley https://doi.org/10.1096/fasebj.31.1_supplement.715.1 2024-05-03T11:58:15Z 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 Article in Journal/Newspaper Orca Wiley Online Library The FASEB Journal 31 S1 |
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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 |
format |
Article in Journal/Newspaper |
author |
Kener, Kyle B Ray, Jason D. Ballard, Matthew Utsch, Will Tessem, Jeffery Sivert |
spellingShingle |
Kener, Kyle B Ray, Jason D. Ballard, Matthew Utsch, Will Tessem, Jeffery Sivert Determining the Role of CEBP/α in Functional β‐cell Mass |
author_facet |
Kener, Kyle B Ray, Jason D. Ballard, Matthew Utsch, Will Tessem, Jeffery Sivert |
author_sort |
Kener, Kyle B |
title |
Determining the Role of CEBP/α in Functional β‐cell Mass |
title_short |
Determining the Role of CEBP/α in Functional β‐cell Mass |
title_full |
Determining the Role of CEBP/α in Functional β‐cell Mass |
title_fullStr |
Determining the Role of CEBP/α in Functional β‐cell Mass |
title_full_unstemmed |
Determining the Role of CEBP/α in Functional β‐cell Mass |
title_sort |
determining the role of cebp/α in functional β‐cell mass |
publisher |
Wiley |
publishDate |
2017 |
url |
http://dx.doi.org/10.1096/fasebj.31.1_supplement.715.1 |
genre |
Orca |
genre_facet |
Orca |
op_source |
The FASEB Journal volume 31, issue S1 ISSN 0892-6638 1530-6860 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1096/fasebj.31.1_supplement.715.1 |
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The FASEB Journal |
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31 |
container_issue |
S1 |
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1800759364905074688 |