ArticleGenes & development2007
Expansion of adult beta-cell mass in response to increased metabolic demand is dependent on HNF-4alpha.
Article in Genes & development, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed.
- Gestational diabetes promotes future maternal cardiovascular disease through endothelin activation and suppressed NO/cGMP/PRKG and AMPK/SIRT1 signaling pathways.American journal of physiology. Heart and circulatory physiology · 2026Article
- Advances and challenges in the mechanistic understanding of beta-cell dysfunction in gestational diabetes mellitus.Journal of animal science · 2026Review
- Article
- Moderate beta-cell ablation triggers synergic compensatory mechanisms even in the absence of overt metabolic disruption.Communications biology · 2024Article
- Hepatocyte nuclear factor 4-α is necessary for high fat diet-induced pancreatic β-cell mass expansion and metabolic compensations.Frontiers in endocrinology · 2024Article
- Maternal diet during pregnancy and adaptive changes in the maternal and fetal pancreas have implications for future metabolic health.Frontiers in endocrinology · 2024Review
- The protein architecture and allosteric landscape of HNF4α.Frontiers in endocrinology · 2023Review
- Dysregulation of β-Cell Proliferation in Diabetes: Possibilities of Combination Therapy in the Development of a Comprehensive Treatment.Biomedicines · 2022Review
- Functional screen of inflammatory bowel disease genes reveals key epithelial functions.Genome medicine · 2021Article
- TRPM7 is a crucial regulator of pancreatic endocrine development and high-fat-diet-induced β-cell proliferation.Development (Cambridge, England) · 2021Article
- Review
- Chromogranin A-positive hormone-negative endocrine cells in pancreas in human pregnancy.Endocrinology, diabetes & metabolism · 2021Article
- Diabetes during Pregnancy: A Maternal Disease Complicating the Course of Pregnancy with Long-Term Deleterious Effects on the Offspring. A Clinical Review.International journal of molecular sciences · 2021Review
- Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer CellsFrontiers in oncology · 2021Article
- Chemical Starting Matter for HNF4α Ligand Discovery and Chemogenomics.International journal of molecular sciences · 2020Article
- Late Cognitive Consequences of Gestational Diabetes to the Offspring, in a New Mouse Model.Molecular neurobiology · 2019Article
- MafB Is Important for Pancreatic β-Cell Maintenance under a MafA-Deficient Condition.Molecular and cellular biology · 2019Article
- LC‑MS/MS proteomic analysis revealed novel associations of 37 proteins with T2DM and notable upregulation of immunoglobulins.International journal of molecular medicine · 2019Article
- Article
- Maternal β-Cell Adaptations in Pregnancy and Placental Signalling: Implications for Gestational Diabetes.International journal of molecular sciences · 2018Review
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
The failure to expand functional pancreatic beta-cell mass in response to increased metabolic demand is a hallmark of type 2 diabetes. Lineage tracing studies indicate that replication of existing beta-cells is the principle mechanism for beta-cell expansion in adult mice. Here we demonstrate that the proliferative response of beta-cells is dependent on the orphan nuclear receptor hepatocyte nuclear factor-4alpha (HNF-4alpha), the gene that is mutated in Maturity-Onset Diabetes of the Young 1 (MODY1). Computational analysis of microarray expression profiles from isolated islets of mice lacking HNF-4alpha in pancreatic beta-cells reveals that HNF-4alpha regulates selected genes in the beta-cell, many of which are involved in proliferation. Using a physiological model of beta-cell expansion, we show that HNF-4alpha is required for beta-cell replication and the activation of the Ras/ERK signaling cascade in islets. This phenotype correlates with the down-regulation of suppression of tumorigenicity 5 (ST5) in HNF-4alpha mutants, which we identify as a novel regulator of ERK phosphorylation in beta-cells and a direct transcriptional target of HNF-4alpha in vivo. Together, these results indicate that HNF-4alpha is essential for the physiological expansion of adult beta-cell mass in response to increased metabolic demand.
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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.