ArticleDiabetologia2012
Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Pharmacometabolomics of sulfonylureas in patients with type 2 diabetes: a cross-sectional study.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Article
- Regeneration of Pancreatic Beta Cells by Modulation of Molecular Targets Using Plant-Derived Compounds: Pharmacological Mechanisms and Clinical Potential.Current issues in molecular biology · 2023Review
- Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies.Frontiers in endocrinology · 2023Review
- Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life.International journal of molecular sciences · 2022Review
- Novel roles of mTORC2 in regulation of insulin secretion by actin filament remodeling.American journal of physiology. Endocrinology and metabolism · 2022Article
- AKT1 Regulates Endoplasmic Reticulum Stress and Mediates the Adaptive Response of Pancreatic β Cells.Molecular and cellular biology · 2020Article
- The Biology of Physiological Health.Cell · 2020Review
- Article
- MicroRNAs 106b and 222 Improve Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes via Pancreatic β-Cell Proliferation.EBioMedicine · 2017Article
- Deletion of β-Arrestin2 in Mice Limited Pancreatic β-Cell Expansion under Metabolic Stress through Activation of the JNK Pathway.Molecular medicine (Cambridge, Mass.) · 2016Article
- Glucose Induces Mouse β-Cell Proliferation via IRS2, MTOR, and Cyclin D2 but Not the Insulin Receptor.Diabetes · 2016Article
- Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes.Molecular metabolism · 2016Article
- Beneficial Renal and Pancreatic Phenotypes in a Mouse Deficient in FXYD2 Regulatory Subunit of Na,K-ATPase.Frontiers in physiology · 2016Review
- Exposure of mouse embryonic pancreas to metformin enhances the number of pancreatic progenitors.Diabetologia · 2014Article
- CCCTC-binding factor mediates effects of glucose on beta cell survival.Cell proliferation · 2014Article
- Upregulation of p21 activates the intrinsic apoptotic pathway in β-cells.American journal of physiology. Endocrinology and metabolism · 2013Article
- Beta cell dysfunction and insulin resistance.Frontiers in endocrinology · 2013Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
aims/hypothesisThe ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B(Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt(caAkt (Tg)) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A (p21(Cip)). In the present study, we sought to assess the mechanisms responsible for augmented p21(Cip) levels in caAkt(Tg) mice and test the role of p21(Cip) in the proliferative responses induced by activation of Akt signalling.
methodsTo gain a greater understanding of the relationship between Akt and p21(Cip), we evaluated the mechanisms involved in the modulation of p2(Cip) by Akt and the in vivo role of reduced p21(Cip) in proliferative responses induced by Akt.
resultsOur experiments showed that Akt signalling regulates p21(Cip) transcription and protein stability. caAkt(Tg) /p21(Cip+/-) mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAkt(Tg) mice. Glucose tolerance tests revealed improved glucose tolerance in caAkt(Tg)/p21(Cip+/-) mice compared with caAkt (Tg). These changes resulted from increased proliferation, survival and beta cell mass in caAkt(Tg)/p21(Cip+/-) compared with caAkt(Tg) mice. CONCLUSIONS/
interpretationOur data indicate that increased p21(Cip) levels in caAkt(Tg) mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that p21(Cip) could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance.
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Registered trials
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