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Title

Transgenic overexpression of the transcription factor Nkx6.1 in β-cells of mice does not increase β-cell proliferation, β-cell mass, or improve glucose clearance

Authors
Schaffer, Ashleigh E
Yang, Almira J
Sander, Maike
Published in Molecular Endocrinology. 2011, vol. 25, no. 11, p. 1904-14
Abstract The loss or dysfunction of the pancreatic endocrine β-cell results in diabetes. Recent innovative therapeutic approaches for diabetes aim to induce β-cell proliferation in vivo by pharmacological intervention. Based on the finding that overexpression of the transcription factor Nkx6.1 in islets in vitro increases β-cell proliferation while maintaining β-cell function, Nkx6.1 has been proposed as a potential target for diabetes therapy. However, it is unknown whether elevated Nkx6.1 levels in β-cells in vivo have similar effects as observed in isolated islets. To this end, we sought to investigate whether overexpression of Nkx6.1 in β-cells in vivo could increase β-cell mass and/or improve β-cell function in normal or β-cell-depleted mice. Using a bigenic inducible Cre-recombinase-based transgenic model, we analyzed the effects of Nkx6.1 overexpression on β-cell proliferation, β-cell mass, and glucose metabolism. We found that mice overexpressing Nkx6.1 in β-cells displayed similar β-cell proliferation rates and β-cell mass as control mice. Furthermore, after partial β-cell ablation, Nkx6.1 overexpression was not sufficient to induce β-cell regeneration under either nondiabetic or diabetic conditions. Together these results demonstrate that sustained Nkx6.1 overexpression in vivo does not stimulate β-cell proliferation, expand β-cell mass, or improve glucose metabolism in either normal or β-cell-depleted pancreata. Thus, raising cellular Nkx6.1 levels in β-cells in vivo is unlikely to have a positive impact on type 2 diabetes.
Keywords AnimalsCell ProliferationEnzyme-Linked Immunosorbent AssayFluorescent Antibody TechniqueGlucose/metabolismHomeodomain Proteins/genetics/metabolismImmunoblottingInsulin-Secreting Cells/cytology/metabolismMiceMice, Transgenic
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PMID: 21964593
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Article (Published version) (2.3 MB) - public document Free access
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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SCHAFFER, Ashleigh E et al. Transgenic overexpression of the transcription factor Nkx6.1 in β-cells of mice does not increase β-cell proliferation, β-cell mass, or improve glucose clearance. In: Molecular Endocrinology, 2011, vol. 25, n° 11, p. 1904-14. https://archive-ouverte.unige.ch/unige:25631

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Deposited on : 2013-01-17

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