| First Author | Annes JP | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 10 | Pages | 3915-20 |
| PubMed ID | 22345561 | Mgi Jnum | J:182148 |
| Mgi Id | MGI:5314835 | Doi | 10.1073/pnas.1201149109 |
| Citation | Annes JP, et al. (2012) Adenosine kinase inhibition selectively promotes rodent and porcine islet beta-cell replication. Proc Natl Acad Sci U S A 109(10):3915-20 |
| abstractText | Diabetes is a pathological condition characterized by relative insulin deficiency, persistent hyperglycemia, and, consequently, diffuse micro- and macrovascular disease. One therapeutic strategy is to amplify insulin-secretion capacity by increasing the number of the insulin-producing beta cells without triggering a generalized proliferative response. Here, we present the development of a small-molecule screening platform for the identification of molecules that increase beta-cell replication. Using this platform, we identify a class of compounds [adenosine kinase inhibitors (ADK-Is)] that promote replication of primary beta cells in three species (mouse, rat, and pig). Furthermore, the replication effect of ADK-Is is cell type-selective: treatment of islet cell cultures with ADK-Is increases replication of beta cells but not that of alpha cells, PP cells, or fibroblasts. Short-term in vivo treatment with an ADK-I also increases beta-cell replication but not exocrine cell or hepatocyte replication. Therefore, we propose ADK inhibition as a strategy for the treatment of diabetes. |
