| First Author | Ye R | Year | 2016 |
| Journal | Mol Metab | Volume | 5 |
| Issue | 7 | Pages | 437-448 |
| PubMed ID | 27408770 | Mgi Jnum | J:268878 |
| Mgi Id | MGI:6272514 | Doi | 10.1016/j.molmet.2016.05.001 |
| Citation | Ye R, et al. (2016) Autonomous interconversion between adult pancreatic alpha-cells and beta-cells after differential metabolic challenges. Mol Metab 5(7):437-448 |
| abstractText | BACKGROUND: Evidence hints at the ability of beta-cells to emerge from non-beta-cells upon genetic or pharmacological interventions. However, their quantitative contributions to the process of autonomous beta-cell regeneration without genetic or pharmacological manipulations remain to be determined. METHODS & RESULTS: Using PANIC-ATTAC mice, a model of titratable, acute beta-cell apoptosis capable of autonomous, and effective islet mass regeneration, we demonstrate that an extended washout of residual tamoxifen activity is crucial for beta-cell lineage tracing studies using the tamoxifen-inducible Cre/loxP systems. We further establish a doxycycline-inducible system to label different cell types in the mouse pancreas and pursued a highly quantitative assessment to trace adult beta-cells after various metabolic challenges. Beyond proliferation of pre-existing beta-cells, non-beta-cells contribute significantly to the post-challenge regenerated beta-cell pool. alpha-cell trans-differentiation is the predominant mechanism upon post-apoptosis regeneration and multiparity. No contributions from exocrine acinar cells were observed. During diet-induced obesity, about 25% of alpha-cells arise de novo from beta-cells. Ectopic expression of Nkx6.1 promotes alpha-to-beta conversion and insulin production. CONCLUSIONS: We identify the origins and fates of adult beta-cells upon post-challenge upon autonomous regeneration of islet mass and establish the quantitative contributions of the different cell types using a lineage tracing system with high temporal resolution. |
