Molecule That Promotes Beta Cell Regeneration Discovered

Restoring a sufficient number of beta cells is critical to reversing and curing T1D. So a key JDRF priority is identifying molecules and factors that promote beta cell regeneration. However, this process is often slow and time-consuming. Dr. Didier Stainier and his colleagues at the University of California, San Francisco developed a fast screening strategy using specially engineered fish embryos to accelerate the normal process of finding an active drug candidate. Using this engineered fish embryo system allowed rapid screening of available compounds to find those that increased beta cell regeneration. The group used this novel system to evaluate 7,000 known, biologically active compounds and identified five that were able to improve beta cell regeneration in this model. The most potent of the five positive compounds was one called NECA. In order to determine the therapeutic potential of NECA, the group then tested its effects on adult mouse islets and in diabetic mice. As predicted by the screening experiments, NECA treatment increased the proliferation of mouse beta cells and increased beta cell numbers which translated into improved glycemic control in diabetic mice.

Reference:

Andersson, O., Adams, BA., Yoo, D. et al. (2012). Adenosine signaling promotes regeneration of pancreatic ² cells in vivo. Cell Metab 15, 885-894.

Investigators and Institutions:

This work was led by Dr. Didier Stainier at UCSF, in collaboration with Dr. Michael German at UCSF.

Ramifications for Individuals with Type 1 Diabetes:

This early stage work identified a new pathway that could be the focus of a drug development effort to promote beta cell regeneration in T1D. However, more work is required to determine if the pathway is effective on human islets, if the pathway could be activated safely in a therapeutic setting, and if suitable drugs can be developed that target the pathway.

JDRF Involvement:

This work was supported, in part, by a JDRF grant to Dr. Stainier, a JDRF Advanced Postdoctoral Fellowship to Dr. Anderson and a JDRF Scholar Award to Dr. German.