ArticleIslets
GSK-3 inactivation or depletion promotes β-cell replication via down regulation of the CDK inhibitor, p27 (Kip1).
Article in Islets. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Txnip deficiency promotes β-cell proliferation in the HFD-induced obesity mouse model.Endocrine connections · 2022Article
- Isoform-Specific Role of GSK-3 in High Fat Diet Induced Obesity and Glucose Intolerance.Cells · 2022Article
- Decreased proliferation of aged rat beta cells corresponds with enhanced expression of the cell cycle inhibitor p27Biology of the cell · 2021Article
- Anti-Angiogenic Properties of Ginsenoside Rg3 Epimers: In Vitro Assessment of Single and Combination Treatments.Cancers · 2021Article
- Regulation of Body Size and Growth Control.Genetics · 2020Review
- MicroRNAs 106b and 222 Improve Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes via Pancreatic β-Cell Proliferation.EBioMedicine · 2017Article
- miR-422a inhibits cell proliferation in colorectal cancer by targeting AKT1 and MAPK1.Cancer cell international · 2017Article
- GSK3β regulates milk synthesis in and proliferation of dairy cow mammary epithelial cells via the mTOR/S6K1 signaling pathway.Molecules (Basel, Switzerland) · 2014Article
- Pancreatic β-cell proliferation in obesity.Advances in nutrition (Bethesda, Md.) · 2014Review
- Small-molecule inhibition of inflammatory β-cell death.Diabetes, obesity & metabolism · 2013Review
- TGF-β Signaling Regulates Pancreatic β-Cell Proliferation through Control of Cell Cycle Regulator p27 Expression.Acta histochemica et cytochemica · 2013Article
- Role of PI3K-AKT-mTOR and Wnt Signaling Pathways in Transition of G1-S Phase of Cell Cycle in Cancer Cells.Frontiers in oncology · 2013Article
- Methylglyoxal impairs insulin signalling and insulin action on glucose-induced insulin secretion in the pancreatic beta cell line INS-1E.Diabetologia · 2011Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Diabetes (T1DM and T2DM) is characterized by a deficit in β-cell mass. A broader understanding of human β-cell replication mechanism is thus important to increase β-cell proliferation for future therapeutic interventions. Here, we show that p27 (Kip1), a CDK inhibitor, is expressed abundantly in isolated adult human islets and interacts with various positive cell cycle regulatory proteins including D-type cyclins (D1, D2 and D3) and their kinase partners, CDK4 and CDK6. Also, we see interaction of cyclin E and its kinase partner, CDK2, with p27 suggesting a critical role of p27 as a negative cell cycle regulator in human islets. Our data demonstrate interaction of p27 with GSK-3 in β-cells and show, employing rodent β-cells (INS-1), isolated human islets and purified β-cells derived from human islets, that siRNA-mediated depletion of GSK-3 or p27 or 1-AKP / BIO - mediated GSK-3 inhibition results in increased β-cell proliferation. We also see reduction of p27 levels following GSK-3 inactivation or depletion. Our data show that serum induction of quiescent INS-1 cells leads to sequential phosphorylation of p27 on its S10 and T187 residues with faster kinetics for S10 corresponding with the decreased levels of p27. Altogether our findings indicate that p27 levels in β-cells are stabilized by GSK-3 and thus p27 down regulation following GSK-3 depletion / inactivation plays a critical role in promoting β-cell replication.
Indexed as
Identifiers
What OpenQuestion holds
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.