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Adenosine kinase inhibition selectively promotes rodent and porcine islet beta-cell replication PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Annes, J. P., Ryu, J. H., Lam, K., Carolan, P. J., Utz, K., Hollister-Lock, J., Arvanites, A. C., Rubin, L. L., Weir, G., Melton, D. A. 2012; 109 (10): 3915-3920

Abstract

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 ß 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 ß-cell replication. Using this platform, we identify a class of compounds [adenosine kinase inhibitors (ADK-Is)] that promote replication of primary ß 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 ß cells but not that of a cells, PP cells, or fibroblasts. Short-term in vivo treatment with an ADK-I also increases ß-cell replication but not exocrine cell or hepatocyte replication. Therefore, we propose ADK inhibition as a strategy for the treatment of diabetes.

View details for DOI 10.1073/pnas.1201149109

View details for Web of Science ID 000301117700063

View details for PubMedID 22345561

View details for PubMedCentralID PMC3309788