| First Author | Taylor BL | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 3 | Pages | 897-903 |
| PubMed ID | 25277396 | Mgi Jnum | J:252878 |
| Mgi Id | MGI:5924390 | Doi | 10.2337/db14-0684 |
| Citation | Taylor BL, et al. (2015) Postnatal beta-cell proliferation and mass expansion is dependent on the transcription factor Nkx6.1. Diabetes 64(3):897-903 |
| abstractText | All forms of diabetes are characterized by a loss of functional beta-cell mass, and strategies for expanding beta-cell mass could have significant therapeutic benefit. We have recently identified the transcription factor Nkx6.1 as an essential maintenance factor of the functional beta-cell state. In addition, Nkx6.1 has been proposed to control beta-cell proliferation, but a role for Nkx6.1 in regulating beta-cell mass has not been demonstrated. Here, we show that Nkx6.1 is required for postnatal beta-cell mass expansion. Genetic inactivation of Nkx6.1 in newly formed beta-cells caused a drastic decrease in early postnatal beta-cell proliferation, leading to reduced beta-cell mass and glucose intolerance. Interestingly, Nkx6.1 was dispensable for prenatal beta-cell proliferation. We found that Nkx6.1 regulates the expression of several beta-cell maturation markers as well as expression of the nutrient sensors Glut2 and Glp1r. Manifestation of the beta-cell mass defect at the transition to postnatal feeding suggests that Nkx6.1 could regulate beta-cell growth by enabling beta-cells to respond to nutrient-dependent proliferation signals, such as glucose and Glp1. Identification of beta-cell-intrinsic regulators that connect nutrient-sensing and proliferation suggests new therapeutic targets for expanding functional beta-cell mass. |
