ArticleDiabetologia2007
MAFA controls genes implicated in insulin biosynthesis and secretion.
Article in Diabetologia, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 200 citations in OpenAlex.
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- Advancing diabetes management: Exploring pancreatic beta-cell restoration's potential and challenges.World journal of gastroenterology · 2024Review
- scParser: sparse representation learning for scalable single-cell RNA sequencing data analysis.Genome biology · 2024Article
- Human pluripotent stem cell-derived β cells: Truly immature islet β cells for type 1 diabetes therapy?World journal of stem cells · 2023Review
- Hepatic insulin synthesis increases in rat models of diabetes mellitus type 1 and 2 differently.PloS one · 2023Article
- Comprehensive Search for GPCR Compounds which Can Enhance MafA and/or PDX-1 Expression Levels Using a Small Molecule Compound Library.Journal of diabetes research · 2023Article
- Importance of multiple endocrine cell types in islet organoids for type 1 diabetes treatment.Translational research : the journal of laboratory and clinical medicine · 2022Review
- Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells.Cell regeneration (London, England) · 2022Review
- In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model.International journal of molecular sciences · 2022Article
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- MafA Regulation in β-Cells: From Transcriptional to Post-Translational Mechanisms.Biomolecules · 2022Review
- Mechanistic Investigation of GHS-R Mediated Glucose-Stimulated Insulin Secretion in Pancreatic Islets.Biomolecules · 2022Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
aims/hypothesisEffects of the transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA) on the regulation of beta cell gene expression and function were investigated. MATERIALS AND
methodsINS-1 stable cell lines permitting inducible up- or downregulation of this transcription factor were established.
resultsMAFA overproduction enhanced and its dominant-negative mutant (DN-MAFA) diminished binding of the factor to the insulin promoter, correlating with insulin mRNA levels and cellular protein content. Glucose-stimulated insulin secretion was facilitated by MAFA and blunted by DN-MAFA. This is partly due to alterations in glucokinase production, the glucose sensor of beta cells. In addition, the expression of important beta cell genes, e.g. those encoding solute carrier family 2 (facilitated glucose transporter), member 2 (formerly known as GLUT2), pancreatic and duodenal homeobox factor 1 (PDX1), NK6 transcription factor-related, locus 1 (NKX6-1), glucagon-like peptide 1 receptor (GLP1R), prohormone convertase 1/3 (PCSK1) and pyruvate carboxylase (PC), was regulated positively by MAFA and negatively by DN-MAFA. CONCLUSIONS/
interpretationThe data suggest that MAFA is not only a key activator of insulin transcription, but also a master regulator of genes implicated in maintaining beta cell function, in particular metabolism-secretion coupling, proinsulin processing and GLP1R signalling. Our in vitro study provides molecular targets that explain the phenotype of recently reported Mafa-null mice. We also demonstrate that MAFA is produced specifically in beta cells of human islets. Glucose influenced DNA-binding activity of MAFA in rat islets in a bell-shaped manner. MAFA thus qualifies as a master regulator of beta-cell-specific gene expression and function.
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Registered trials
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.