Adenosine kinase inhibition selectively promotes rodent and porcine islet β-cell replication
Annes, J. P.
Ryu, J. H.
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CitationAnnes, J. P., J. H. Ryu, K. Lam, P. J. Carolan, K. Utz, J. Hollister-Lock, A. C. Arvanites, L. L. Rubin, G. Weir, and D. A. Melton. 2012. “Adenosine Kinase Inhibition Selectively Promotes Rodent and Porcine Islet β-Cell Replication.” Proceedings of the National Academy of Sciences 109 (10) (March 6): 3915–3920. doi:10.1073/pnas.1201149109.
AbstractDiabetes 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 β 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 β-cell replication. Using this platform, we identify a class of compounds [adenosine kinase inhibitors (ADK-Is)] that promote replication of primary β 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 β cells but not that of α cells, PP cells, or fibroblasts. Short-term in vivo treatment with an ADK-I also increases β-cell replication but not exocrine cell or hepatocyte replication. Therefore, we propose ADK inhibition as a strategy for the treatment of diabetes.
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