Identifying chemical compounds or small molecules capable of inducing a desired biological response is often the first step in developing new drugs. Robotic screening methods allow rapid and parallel testing of hundreds of thousands to millions of compounds to find the few that will have the desired effect. This report describes a screening strategy to identify small molecules that induce replication of beta cells. In a pilot screen of approximately 850 known bio-active small molecules, the researchers identified two compounds that induced beta cell proliferation in rodents and pigs. Both compounds are well-characterized inhibitors of the enzyme adenosine kinase. This replicative effect was found to be unique to beta cells suggesting for the first time that this enzyme plays a unique role in beta cells.
Annes, JP, Hyoje Ryu, J, Lama, K, Carolana, PJ, Utza, K, Hollister-Lockd, J, Arvanitesa, AC, Rubina, LL, Weird, G,and Melton, DA. (2012). Adenosine kinase inhibition selectively promotes rodent and porcine islet beta-cell replication. Proc. Natl. Acad. Sci. USA. March 6, 109(10):3915-3920.
Ramifications for Individuals with Type 1 Diabetes:
This work describes a method for screening for chemicals that can induce beta cell proliferation and the discovery of a novel class of small molecules that is capable of inducing beta cell replication in a laboratory setting. Future efforts will be aimed at determining if the chemicals identified are suitable for development as drugs or therapeutics to help restore beta cell mass in individuals with T1D and identifying additional chemicals capable of inducing beta cell replication.