| First Author | Wang ZV | Year | 2008 |
| Journal | Diabetes | Volume | 57 |
| Issue | 8 | Pages | 2137-48 |
| PubMed ID | 18469203 | Mgi Jnum | J:141693 |
| Mgi Id | MGI:3819285 | Doi | 10.2337/db07-1631 |
| Citation | Wang ZV, et al. (2008) PANIC-ATTAC: a mouse model for inducible and reversible beta-cell ablation. Diabetes 57(8):2137-48 |
| abstractText | OBJECTIVE: Islet transplantations have been performed clinically, but their practical applications are limited. An extensive effort has been made toward the identification of pancreatic beta-cell stem cells that has yielded many insights to date, yet targeted reconstitution of beta-cell mass remains elusive. Here, we present a mouse model for inducible and reversible ablation of pancreatic beta-cells named the PANIC-ATTAC (pancreatic islet beta-cell apoptosis through targeted activation of caspase 8) mouse. RESEARCH DESIGN AND METHODS: We efficiently induce beta-cell death through apoptosis and concomitant hyperglycemia by administration of a chemical dimerizer to the transgenic mice. In contrast to animals administered streptozotocin, the diabetes phenotype and beta-cell loss are fully reversible in the PANIC-ATTAC mice, and we find significant beta-cell recovery with normalization of glucose levels after 2 months. RESULTS: The rate of recovery can be enhanced by various pharmacological interventions with agents acting on the glucagon-like peptide 1 axis and agonists of peroxisome proliferator-activated receptor-gamma. During recovery, we find an increased population of GLUT2(+)/insulin(-) cells in the islets of PANIC-ATTAC mice, which may represent a novel pool of potential beta-cell precursors. CONCLUSIONS: The PANIC-ATTAC mouse may be used as an animal model of inducible and reversible beta-cell ablation and therefore has applications in many areas of diabetes research that include identification of beta-cell precursors, evaluation of glucotoxicity effects in diabetes, and examination of pharmacological interventions. |
