ArticleJournal of diabetes research2016
Cdk5r1 Overexpression Induces Primary β-Cell Proliferation.
Article in Journal of diabetes research, 2016. 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, 20 citations in OpenAlex.
- Nr4a1 β-cell specific deletion impairs glucose tolerance in female mice.American journal of physiology. Endocrinology and metabolism · 2026Article
- A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics.Nature communications · 2025Article
- RNA m6A dynamic modification mediated by nucleus-localized FTO is involved in follicular reserve.Zoological research · 2024Article
- Structural insights into the ubiquitylation strategy of the oligomeric CRL2The EMBO journal · 2024Article
- Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic Health.Metabolites · 2023Article
- Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions.Biomolecules · 2021Article
- Decreased proliferation of aged rat beta cells corresponds with enhanced expression of the cell cycle inhibitor p27Biology of the cell · 2021Article
- Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues.Cells · 2019Review
- Common gut microbial metabolites of dietary flavonoids exert potent protective activities in β-cells and skeletal muscle cells.The Journal of nutritional biochemistry · 2018Article
- High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds.Journal of visualized experiments : JoVE · 2018Article
- The Orphan Nuclear Receptor 4A1: A Potential New Therapeutic Target for Metabolic Diseases.Journal of diabetes research · 2018Review
- Candidate genes responsible for early key events of phenobarbital-promoted mouse hepatocellular tumorigenesis based on differentiation of regulating genes between wild type mice and humanized chimeric mice.Toxicology research · 2017Article
- Replicative capacity of β-cells and type 1 diabetes.Journal of autoimmunity · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Decreased β-cell mass is a hallmark of type 1 and type 2 diabetes. Islet transplantation as a method of diabetes therapy is hampered by the paucity of transplant ready islets. Understanding the pathways controlling islet proliferation may be used to increase functional β-cell mass through transplantation or by enhanced growth of endogenous β-cells. We have shown that the transcription factor Nkx6.1 induces β-cell proliferation by upregulating the orphan nuclear hormone receptors Nr4a1 and Nr4a3. Using expression analysis to define Nkx6.1-independent mechanisms by which Nr4a1 and Nr4a3 induce β-cell proliferation, we demonstrated that cyclin-dependent kinase 5 regulatory subunit 1 (Cdk5r1) is upregulated by Nr4a1 and Nr4a3 but not by Nkx6.1. Overexpression of Cdk5r1 is sufficient to induce primary rat β-cell proliferation while maintaining glucose stimulated insulin secretion. Overexpression of Cdk5r1 in β-cells confers protection against apoptosis induced by etoposide and thapsigargin, but not camptothecin. The Cdk5 kinase complex inhibitor roscovitine blocks islet proliferation, suggesting that Cdk5r1 mediated β-cell proliferation is a kinase dependent event. Overexpression of Cdk5r1 results in pRb phosphorylation, which is inhibited by roscovitine treatment. These data demonstrate that activation of the Cdk5 kinase complex is sufficient to induce β-cell proliferation while maintaining glucose stimulated insulin secretion.
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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.