Cyclins D2 and D1 Are Essential for Postnatal Pancreatic β-Cell Growth
Open accessAbstract
Regulation of adult beta-cell mass in pancreatic islets is essential to preserve sufficient insulin secretion in order to appropriately regulate glucose homeostasis. In many tissues mitogens influence development by stimulating D-type cyclins (D1, D2, or D3) and activating cyclin-dependent kinases (CDK4 or CDK6), which results in progression through the G(1) phase of the cell cycle. Here we show that cyclins D2 and D1 are essential for normal postnatal islet growth. In adult murine islets basal cyclin D2 mRNA expression was easily detected, while cyclin D1 was expressed at lower levels and cyclin D3 was nearly undetectable. Prenatal islet development occurred normally in cyclin D2(-/-) or cyclin D1(+/-) D2(-/-) mice. However, beta-cell proliferation, adult mass, and glucose tolerance were decreased in adult cyclin D2(-/-) mice, causing glucose intolerance that progressed to diabetes by 12 months of age. Although cyclin D1(+/-) mice never developed diabetes, life-threatening diabetes developed in 3-month-old cyclin D1(-/+) D2(-/-) mice as beta-cell mass decreased after birth. Thus, cyclins D2 and D1 were essential for beta-cell expansion in adult mice. Strategies to tightly regulate D-type cyclin activity in beta cells could prevent or cure diabetes.
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During physiological growth in humans, mice and other species, juvenile β-cells expand by self-renewal while maintaining their hallmark functions.
“During physiological growth in humans, mice and other species, juvenile β-cells expand by self-renewal7,8 while maintaining their hallmark functions.”
From PDGF signalling controls age-dependent proliferation in pancreatic β-cells (2011) · cites this paper as [8]
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- Authors
- Kushner, J. A., Ciemerych, M. A., Sicinska, E., Wartschow, L. M., Teta, M., Long, S. Y., Sicinski, P., & White, M. F.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Harvard University (US)
- Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115
- Howard Hughes Medical Institute (US)
- Corresponding author
- Kushner, Jake A.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2005-05-01
- Volume
- 25
- Issue
- 9
- Pages
- 3752-3762
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1084308
- OpenAlex
- W1969459168
- Cited by
- 334
- References
- 32
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 7 · 2023: 4 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 13 · 2018: 9 · 2017: 18 · 2016: 16 · 2015: 17 · 2014: 16 · 2013: 21 · 2012: 21
- FWCI
- 28.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Charles H. Hood Foundation
- Kosciuszko Foundation
- Pediatric Endocrine Society
- National Institutes of Health (5k11dk002024-02, DK38712)
- National Cancer Institute (R01CA083688)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK55326, DK 43808, R01DK055326, DK 38712, DK 02024, R01DK038712, DK 064101, K08DK064101, R01DK043808)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- cyclin D2, cyclin D1, cyclin D3, pancreatic beta-cell proliferation, beta-cell mass, impaired glucose tolerance, diabetes mellitus, CDK4, CDK6, G1 cell cycle, pancreatic islets
- MeSH terms
- Animals, Blood Glucose, Diabetes Mellitus, Glucagon, Insulin, Islets of Langerhans, Male, Gene Expression, Cyclins, Glucose Intolerance, Mice, Knockout, Cyclin D1, Cell Proliferation, Mice, Cyclin D2
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