ArticleMolecular endocrinology (Baltimore, Md.)2013
Preventing p38 MAPK-mediated MafA degradation ameliorates β-cell dysfunction under oxidative stress.
Article in Molecular endocrinology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Stimulation to secrete insulin induces pancreatic β-cell dysfunction through Tfe3 activation.iScience · 2026Article
- Cross-sectional associations between plasma copper, zinc and prediabetes among rural Indian adolescent girls: baseline data from the DERVAN cohort (DERVAN-8).Journal of biosciences · 2026Article
- Is it possible for type 2 diabetic patients with low level of copper to have better glycemic control under different apolipoprotein B levels?Frontiers in endocrinology · 2026Article
- Enhanced Insulin Secretion Through Upregulation of Transcription Factors by Hydroalcoholic Extract of Securigera securidaca Seeds in Diabetic Animal Model.Endocrinology, diabetes & metabolism · 2024Article
- The association between serum copper concentration and prevalence of diabetes among US adults with hypertension (NHANES 2011-2016).Journal of cellular and molecular medicine · 2024Article
- Effect of hydroalcoholic seed extract of Nigella sativa on hepatic and pancreatic factors of Nrf2 and FGF21 in the regulation of insulin transcription factors of MafA and PDX-1 in streptozotocin-treated diabetic rats.Nutrition & metabolism · 2022Article
- Role of the Transcription Factor MAFA in the Maintenance of Pancreatic β-Cells.International journal of molecular sciences · 2022Review
- MafA Regulation in β-Cells: From Transcriptional to Post-Translational Mechanisms.Biomolecules · 2022Review
- The Association Between Plasma Copper Concentration and Prevalence of Diabetes in Chinese Adults With Hypertension.Frontiers in public health · 2022Article
- Redox Homeostasis in Pancreatic β-Cells: From Development to Failure.Antioxidants (Basel, Switzerland) · 2021Review
- Oxidative stress and diabetes: antioxidative strategies.Frontiers of medicine · 2020Review
- Interactions between plasma copper concentrations and SOD1 gene polymorphism for impaired glucose regulation and type 2 diabetes.Redox biology · 2019Article
- Glucose regulates MafA transcription factor abundance and insulin gene expression by inhibiting AMP-activated protein kinase in pancreatic β-cells.The Journal of biological chemistry · 2018Article
- The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus.Antioxidants & redox signaling · 2017Review
- U-Shaped Association between Plasma Manganese Levels and Type 2 Diabetes.Environmental health perspectives · 2016Article
- Proper activation of MafA is required for optimal differentiation and maturation of pancreatic β-cells.Best practice & research. Clinical endocrinology & metabolism · 2015Review
- Aldosterone induces clonal β-cell failure through glucocorticoid receptor.Scientific reports · 2015Article
- Possible contribution of (pro)renin receptor to development of gestational diabetes mellitus.World journal of diabetes · 2014Review
- Heterozygous SOD2 deletion impairs glucose-stimulated insulin secretion, but not insulin action, in high-fat-fed mice.Diabetes · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The reduction in the expression of glucose-responsive insulin gene transcription factor MafA accompanies the development of β-cell dysfunction under oxidative stress/diabetic milieu. Humans with type 2 diabetes have reduced MafA expression, and thus preventing this reduction could overcome β-cell dysfunction and diabetes. We previously showed that p38 MAPK, but not glycogen synthase kinase 3 (GSK3), is a major regulator of MafA degradation under oxidative stress. Here, we examined the mechanisms of this degradation and whether preventing MafA degradation under oxidative stress will overcome β-cell dysfunction. We show that under oxidative and nonoxidative conditions p38 MAPK directly binds to MafA and triggers MafA degradation via ubiquitin proteasomal pathway. However, unlike nonoxidative conditions, MafA degradation under oxidative stress depended on p38 MAPK-mediated phosphorylation at threonine (T) 134, and not T57. Furthermore the expression of alanine (A) 134-MafA, but not A57-MafA, reduced the oxidative stress-mediated loss of glucose-stimulated insulin secretion, which was independent of p38 MAPK action on protein kinase D, a regulator of insulin secretion. Interestingly, the expression of proteasomal activator PA28γ that degrades GSK3-phosphorylated (including T57) MafA was reduced under oxidative stress, explaining the dominance of p38 MAPK over the GSK3 pathway in regulating MafA stability under oxidative stress. These results identify two distinct pathways mediating p38 MAPK-dependent MafA degradation under oxidative and nonoxidative conditions and show that inhibiting MafA degradation under oxidative stress ameliorates β-cell dysfunction and could lead to novel therapies for diabetes.
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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.