Cdk5r1 Overexpression Induces Primary β-Cell Proliferation
Joint Authors
Draney, Carrie
Hobson, Amanda E.
Grover, Samuel G.
Jack, Benjamin O.
Tessem, Jeffery S.
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-12-14
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Decreased β-cell mass is a hallmark of type 1 and type 2 diabetes.
Islet transplantation as a method of diabetes therapy is hampered by the paucity of transplant ready islets.
Understanding the pathways controlling islet proliferation may be used to increase functional β-cell mass through transplantation or by enhanced growth of endogenous β-cells.
We have shown that the transcription factor Nkx6.1 induces β-cell proliferation by upregulating the orphan nuclear hormone receptors Nr4a1 and Nr4a3.
Using expression analysis to define Nkx6.1-independent mechanisms by which Nr4a1 and Nr4a3 induce β-cell proliferation, we demonstrated that cyclin-dependent kinase 5 regulatory subunit 1 (Cdk5r1) is upregulated by Nr4a1 and Nr4a3 but not by Nkx6.1.
Overexpression of Cdk5r1 is sufficient to induce primary rat β-cell proliferation while maintaining glucose stimulated insulin secretion.
Overexpression of Cdk5r1 in β-cells confers protection against apoptosis induced by etoposide and thapsigargin, but not camptothecin.
The Cdk5 kinase complex inhibitor roscovitine blocks islet proliferation, suggesting that Cdk5r1 mediated β-cell proliferation is a kinase dependent event.
Overexpression of Cdk5r1 results in pRb phosphorylation, which is inhibited by roscovitine treatment.
These data demonstrate that activation of the Cdk5 kinase complex is sufficient to induce β-cell proliferation while maintaining glucose stimulated insulin secretion.
American Psychological Association (APA)
Draney, Carrie& Hobson, Amanda E.& Grover, Samuel G.& Jack, Benjamin O.& Tessem, Jeffery S.. 2015. Cdk5r1 Overexpression Induces Primary β-Cell Proliferation. Journal of Diabetes Research،Vol. 2016, no. 2016, pp.1-15.
https://search.emarefa.net/detail/BIM-1108203
Modern Language Association (MLA)
Draney, Carrie…[et al.]. Cdk5r1 Overexpression Induces Primary β-Cell Proliferation. Journal of Diabetes Research No. 2016 (2016), pp.1-15.
https://search.emarefa.net/detail/BIM-1108203
American Medical Association (AMA)
Draney, Carrie& Hobson, Amanda E.& Grover, Samuel G.& Jack, Benjamin O.& Tessem, Jeffery S.. Cdk5r1 Overexpression Induces Primary β-Cell Proliferation. Journal of Diabetes Research. 2015. Vol. 2016, no. 2016, pp.1-15.
https://search.emarefa.net/detail/BIM-1108203
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1108203