ArticleDiabetologia2014
Dichotomous role of pancreatic HUWE1/MULE/ARF-BP1 in modulating beta cell apoptosis in mice under physiological and genotoxic conditions.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Aberrant activation of p53-TRIB3 axis contributes to diabetic myocardial insulin resistance and sulforaphane protection.Journal of advanced research · 2025Article
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- Transcriptome Changes and Metabolic Outcomes After Bariatric Surgery in Adults With Obesity and Type 2 Diabetes.Journal of the Endocrine Society · 2023Article
- Ubiquitin ligase E3 HUWE1/MULE targets transferrin receptor for degradation and suppresses ferroptosis in acute liver injury.Cell death and differentiation · 2022Article
- RyR2/IRBIT regulates insulin gene transcript, insulin content, and secretion in the insulinoma cell line INS-1.Scientific reports · 2022Article
- Dicarbonyl stress, protein glycation and the unfolded protein response.Glycoconjugate journal · 2021Review
- Regulating tumor suppressor genes: post-translational modifications.Signal transduction and targeted therapy · 2020Review
- Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway.International journal of molecular sciences · 2019Review
- Silencing Huwe1 reduces apoptosis of cortical neurons exposed to oxygen-glucose deprivation and reperfusion.Neural regeneration research · 2019Article
- Peptidome analysis reveals the involvement of endogenous peptides in mouse pancreatic dysfunction with aging.Journal of cellular physiology · 2019Article
- Hepatic PPARα function is controlled by polyubiquitination and proteasome-mediated degradation through the coordinated actions of PAQR3 and HUWE1.Hepatology (Baltimore, Md.) · 2018Article
- HUWE1 controls the development of non-small cell lung cancer through down-regulation of p53.Theranostics · 2018Article
- DPP-4 (CD26) inhibitor sitagliptin exerts anti-inflammatory effects on rat insulinoma (RINm) cells via suppressing NF-κB activation.Endocrine · 2017Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
aims/hypothesisDiabetes 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.
methodsWe 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.
resultsTargeted 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/
interpretationHUWE1 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.