Journal article
Targeted Overexpression of CKI-Insensitive Cyclin-Dependent Kinase 4 Increases Functional β-Cell Number Through Enhanced Self-Replication in Zebrafish
Zebrafish, Vol.10(2), pp.17-176
06/01/2013
Handle:
https://hdl.handle.net/2376/101364
PMCID: PMC3673610
PMID: 23544990
Abstract
β-Cells of the islet of Langerhans produce insulin to maintain glucose homeostasis. Self-replication of β-cells is the predominant mode of postnatal β-cell production in mammals, with about 20% of rodent β cells dividing in a 24-hour period. However, replicating β-cells are rare in adults. Induction of self-replication of existing β-cells is a potential treatment for diabetes. In zebrafish larvae, β-cells rarely self-replicate, even under conditions that favor β-cell genesis such overnutrition and β-cell ablation. It is not clear why larval β-cells are refractory to replication. In this study, we tested the hypothesis that insufficient activity of cyclin-dependent kinase 4 may be responsible for the low replication rate by ectopically expressing in β-cells a mutant CDK4 (CDK4
R24C
) that is insensitive to inhibition by cyclin-dependent kinase inhibitors. Our data show that expression of CDK4
R24C
in β-cells enhanced β-cell replication. CDK4
R24C
also dampened compensatory β-cell neogenesis in larvae and improved glucose tolerance in adult zebrafish. Our data indicate that CDK4 inhibition contributes to the limited β-cell replication in larval zebrafish. To our knowledge, this is the first example of genetically induced β-cell replication in zebrafish.
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Details
- Title
- Targeted Overexpression of CKI-Insensitive Cyclin-Dependent Kinase 4 Increases Functional β-Cell Number Through Enhanced Self-Replication in Zebrafish
- Creators
- Mingyu Li - 1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TennesseeLisette A Maddison - 1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TennesseeZachary Crees - 2College of Medicine, University of Illinois, Chicago, IllinoisWenbiao Chen - 1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee
- Publication Details
- Zebrafish, Vol.10(2), pp.17-176
- Academic Unit
- Center for Reproductive Biology
- Publisher
- Mary Ann Liebert, Inc
- Identifiers
- 99900546673201842
- Language
- English
- Resource Type
- Journal article