File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Dichotomous role of pancreatic HUWE1/MULE/ARF-BP1 in modulating beta cell apoptosis in mice under physiological and genotoxic conditions

TitleDichotomous role of pancreatic HUWE1/MULE/ARF-BP1 in modulating beta cell apoptosis in mice under physiological and genotoxic conditions
Authors
KeywordsBeta cell
Apoptosis
Diabetes
MULE
HUWE1
ARF-BP1
Issue Date2014
Citation
Diabetologia, 2014, v. 57, n. 9, p. 1889-1898 How to Cite?
AbstractAims/hypothesis: Diabetes mellitus represents a significant burden on the health of the global population. Both type 1 and type 2 diabetes share a common feature of a reduction in functional beta cell mass. A newly discovered ubiquitination molecule HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase (HUWE1 [also known as MULE or ARF-BP1]) is a critical regulator of p53-dependent apoptosis. However, its role in islet homeostasis is not entirely clear. Methods: We generated mice with pancreas-specific deletion of Huwe1 using a Cre-loxP recombination system driven by the Pdx1 promoter (Pdx1cre + Huwe1 fl/fl) to assess the in vivo role of HUWE1 in the pancreas. Results: Targeted deletion of Huwe1 in the pancreas preferentially activated p53-mediated beta cell apoptosis, leading to reduced beta cell mass and diminished insulin exocytosis. These defects were aggravated by ageing, with progressive further decline in insulin secretion and glucose homeostasis in older mice. Intriguingly, Huwe1 deletion provided protection against genotoxicity, such that Pdx1cre + Huwe1 fl/fl mice were resistant to multiple-low-dose-streptozotocin-induced beta cell apoptosis and diabetes. Conclusion/interpretation: HUWE1 expression in the pancreas is essential in determining beta cell mass. Furthermore, HUWE1 demonstrated divergent roles in regulating beta cell apoptosis depending on physiological or genotoxic conditions. © 2014 Springer-Verlag Berlin Heidelberg.
Persistent Identifierhttp://hdl.handle.net/10722/292839
ISSN
2023 Impact Factor: 8.4
2023 SCImago Journal Rankings: 3.355
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Linyuan-
dc.contributor.authorLuk, Cynthia T.-
dc.contributor.authorSchroer, Stephanie A.-
dc.contributor.authorSmith, Alannah M.-
dc.contributor.authorLi, Xie-
dc.contributor.authorCai, Erica P.-
dc.contributor.authorGaisano, Herbert-
dc.contributor.authorMacDonald, Patrick E.-
dc.contributor.authorHao, Zhenyue-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorWoo, Minna-
dc.date.accessioned2020-11-17T14:57:19Z-
dc.date.available2020-11-17T14:57:19Z-
dc.date.issued2014-
dc.identifier.citationDiabetologia, 2014, v. 57, n. 9, p. 1889-1898-
dc.identifier.issn0012-186X-
dc.identifier.urihttp://hdl.handle.net/10722/292839-
dc.description.abstractAims/hypothesis: Diabetes mellitus represents a significant burden on the health of the global population. Both type 1 and type 2 diabetes share a common feature of a reduction in functional beta cell mass. A newly discovered ubiquitination molecule HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase (HUWE1 [also known as MULE or ARF-BP1]) is a critical regulator of p53-dependent apoptosis. However, its role in islet homeostasis is not entirely clear. Methods: We generated mice with pancreas-specific deletion of Huwe1 using a Cre-loxP recombination system driven by the Pdx1 promoter (Pdx1cre + Huwe1 fl/fl) to assess the in vivo role of HUWE1 in the pancreas. Results: Targeted deletion of Huwe1 in the pancreas preferentially activated p53-mediated beta cell apoptosis, leading to reduced beta cell mass and diminished insulin exocytosis. These defects were aggravated by ageing, with progressive further decline in insulin secretion and glucose homeostasis in older mice. Intriguingly, Huwe1 deletion provided protection against genotoxicity, such that Pdx1cre + Huwe1 fl/fl mice were resistant to multiple-low-dose-streptozotocin-induced beta cell apoptosis and diabetes. Conclusion/interpretation: HUWE1 expression in the pancreas is essential in determining beta cell mass. Furthermore, HUWE1 demonstrated divergent roles in regulating beta cell apoptosis depending on physiological or genotoxic conditions. © 2014 Springer-Verlag Berlin Heidelberg.-
dc.languageeng-
dc.relation.ispartofDiabetologia-
dc.subjectBeta cell-
dc.subjectApoptosis-
dc.subjectDiabetes-
dc.subjectMULE-
dc.subjectHUWE1-
dc.subjectARF-BP1-
dc.titleDichotomous role of pancreatic HUWE1/MULE/ARF-BP1 in modulating beta cell apoptosis in mice under physiological and genotoxic conditions-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1007/s00125-014-3295-8-
dc.identifier.pmid24981769-
dc.identifier.scopuseid_2-s2.0-84905575097-
dc.identifier.volume57-
dc.identifier.issue9-
dc.identifier.spage1889-
dc.identifier.epage1898-
dc.identifier.eissn1432-0428-
dc.identifier.isiWOS:000340050800020-
dc.identifier.issnl0012-186X-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats