dc.contributor.author |
Dissanayake, Waruni |
en |
dc.contributor.author |
Sorrenson, Brie |
en |
dc.contributor.author |
Lee, Kathryn |
en |
dc.contributor.author |
Barre, Sandra |
en |
dc.contributor.author |
Shepherd, Peter R |
en |
dc.date.accessioned |
2020-05-06T03:54:54Z |
en |
dc.date.issued |
2020-02 |
en |
dc.identifier.citation |
Biochemical journal 477(4):763-772 Feb 2020 |
en |
dc.identifier.issn |
0264-6021 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/50536 |
en |
dc.description.abstract |
The recent finding that β-catenin levels play an important rate-limiting role in processes regulating insulin secretion lead us to investigate whether its binding partner α-catenin also plays a role in this process. We find that levels of both α-E-catenin and α-N-catenin are rapidly up-regulated as levels of glucose are increased in rat clonal β-cell models INS-1E and INS-832/3. Lowering in levels of either α-catenin isoform using siRNA resulted in significant increases in glucose stimulated insulin secretion (GSIS) and this effect was attenuated when β-catenin levels were lowered indicating these proteins have opposing effects on insulin release. This effect of α-catenin knockdown on GSIS was not due to increases in insulin expression but was associated with increases in calcium influx into cells. Moreover, simultaneous depletion of α-E catenin and α-N catenin decreased the actin polymerisation to a similar degree as latrunculin treatment and inhibition of ARP 2/3 mediated actin branching with CK666 attenuated the α-catenin depletion effect on GSIS. This suggests α-catenin mediated actin remodelling may be involved in the regulation of insulin secretion. Together this indicates that α-catenin and β-catenin can play opposing roles in regulating insulin secretion, with some degree of functional redundancy in roles of α-E-catenin and α-N-catenin. The finding that, at least in β-cell models, the levels of each can be regulated in the longer term by glucose also provides a potential mechanism by which sustained changes in glucose levels might impact on the magnitude of GSIS. |
en |
dc.format.medium |
Print |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
The Biochemical journal |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
en |
dc.subject |
Cells, Cultured |
en |
dc.subject |
Animals |
en |
dc.subject |
Rats |
en |
dc.subject |
Glucose |
en |
dc.subject |
Protein Isoforms |
en |
dc.subject |
Sweetening Agents |
en |
dc.subject |
Gene Expression Regulation |
en |
dc.subject |
Insulin-Secreting Cells |
en |
dc.subject |
alpha Catenin |
en |
dc.subject |
Insulin Secretion |
en |
dc.title |
α-catenin isoforms are regulated by glucose and involved in regulating insulin secretion in rat clonal β-cell models. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1042/bcj20190832 |
en |
pubs.issue |
4 |
en |
pubs.begin-page |
763 |
en |
pubs.volume |
477 |
en |
dc.rights.holder |
Copyright: The authors |
en |
pubs.end-page |
772 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
en |
pubs.subtype |
research-article |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
796965 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Molecular Medicine |
en |
dc.identifier.eissn |
1470-8728 |
en |
pubs.record-created-at-source-date |
2020-02-01 |
en |
pubs.dimensions-id |
32003420 |
en |