| First Author | Schaffer AE | Year | 2011 |
| Journal | Mol Endocrinol | Volume | 25 |
| Issue | 11 | Pages | 1904-14 |
| PubMed ID | 21964593 | Mgi Jnum | J:234595 |
| Mgi Id | MGI:5790303 | Doi | 10.1210/me.2011-1010 |
| Citation | Schaffer AE, et al. (2011) Transgenic overexpression of the transcription factor Nkx6.1 in beta-cells of mice does not increase beta-cell proliferation, beta-cell mass, or improve glucose clearance. Mol Endocrinol 25(11):1904-14 |
| abstractText | The loss or dysfunction of the pancreatic endocrine beta-cell results in diabetes. Recent innovative therapeutic approaches for diabetes aim to induce beta-cell proliferation in vivo by pharmacological intervention. Based on the finding that overexpression of the transcription factor Nkx6.1 in islets in vitro increases beta-cell proliferation while maintaining beta-cell function, Nkx6.1 has been proposed as a potential target for diabetes therapy. However, it is unknown whether elevated Nkx6.1 levels in beta-cells in vivo have similar effects as observed in isolated islets. To this end, we sought to investigate whether overexpression of Nkx6.1 in beta-cells in vivo could increase beta-cell mass and/or improve beta-cell function in normal or beta-cell-depleted mice. Using a bigenic inducible Cre-recombinase-based transgenic model, we analyzed the effects of Nkx6.1 overexpression on beta-cell proliferation, beta-cell mass, and glucose metabolism. We found that mice overexpressing Nkx6.1 in beta-cells displayed similar beta-cell proliferation rates and beta-cell mass as control mice. Furthermore, after partial beta-cell ablation, Nkx6.1 overexpression was not sufficient to induce beta-cell regeneration under either nondiabetic or diabetic conditions. Together these results demonstrate that sustained Nkx6.1 overexpression in vivo does not stimulate beta-cell proliferation, expand beta-cell mass, or improve glucose metabolism in either normal or beta-cell-depleted pancreata. Thus, raising cellular Nkx6.1 levels in beta-cells in vivo is unlikely to have a positive impact on type 2 diabetes. |
