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Postnatal β-cell proliferation and mass expansion is dependent on the transcription factor Nkx6.1

Item Type:Article
Title:Postnatal β-cell proliferation and mass expansion is dependent on the transcription factor Nkx6.1
Creators Name:Taylor, B.L. and Benthuysen, J. and Sander, M.
Abstract:All forms of diabetes are characterized by a loss of functional β-cell mass, and strategies for expanding β-cell mass could have significant therapeutic benefit. We have recently identified the transcription factor Nkx6.1 as an essential maintenance factor of the functional β-cell state. In addition, Nkx6.1 has been proposed to control β-cell proliferation, but a role for Nkx6.1 in regulating β-cell mass has not been demonstrated. Here, we show that Nkx6.1 is required for postnatal β-cell mass expansion. Genetic inactivation of Nkx6.1 in newly formed β-cells caused a drastic decrease in early postnatal β-cell proliferation, leading to reduced β-cell mass and glucose intolerance. Interestingly, Nkx6.1 was dispensable for prenatal β-cell proliferation. We found that Nkx6.1 regulates the expression of several β-cell maturation markers as well as expression of the nutrient sensors Glut2 and Glp1r. Manifestation of the β-cell mass defect at the transition to postnatal feeding suggests that Nkx6.1 could regulate β-cell growth by enabling β-cells to respond to nutrient-dependent proliferation signals, such as glucose and Glp1. Identification of β-cell-intrinsic regulators that connect nutrient-sensing and proliferation suggests new therapeutic targets for expanding functional β-cell mass.
Keywords:Cell Proliferation, Homeodomain Proteins, Hyperglycemia, Insulin-Secreting Cells, Animals, Mice
Source:Diabetes
ISSN:0012-1797
Publisher:American Diabetes Association
Volume:64
Number:3
Page Range:897-903
Date:1 March 2015
Official Publication:https://doi.org/10.2337/db14-0684
PubMed:View item in PubMed

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