| First Author | Xiao X | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 4 | Pages | 1217-26 |
| PubMed ID | 23248173 | Mgi Jnum | J:208589 |
| Mgi Id | MGI:5563739 | Doi | 10.2337/db12-1428 |
| Citation | Xiao X, et al. (2013) TGFbeta receptor signaling is essential for inflammation-induced but not beta-cell workload-induced beta-cell proliferation. Diabetes 62(4):1217-26 |
| abstractText | Protection and restoration of a functional beta-cell mass are fundamental strategies for prevention and treatment of diabetes. Consequently, knowledge of signals that determine the functional beta-cell mass is of immense clinical relevance. Transforming growth factor beta (TGFbeta) superfamily signaling pathways play a critical role in development and tissue specification. Nevertheless, the role of these pathways in adult beta-cell homeostasis is not well defined. Here, we ablated TGFbeta receptor I and II genes in mice undergoing two surgical beta-cell replication models (partial pancreatectomy or partial duct ligation), representing two triggers for beta-cell proliferation, increased beta-cell workload and local inflammation, respectively. Our data suggest that TGFbeta receptor signaling is necessary for baseline beta-cell proliferation. By either provision of excess glucose or treatment with exogenous insulin, we further demonstrated that inflammation and increased beta-cell workload are both stimulants for beta-cell proliferation but are TGFbeta receptor signaling dependent and independent, respectively. Collectively, by using a pancreas-specific TGFbeta receptor-deleted mouse model, we have identified two distinct pathways that regulate adult beta-cell proliferation. Our study thus provides important information for understanding beta-cell proliferation during normal growth and in pancreatic diseases. |
