Figure 1. Agonizing b cell regeneration. A paper published by University of California, San Francisco researchers in Cell Metabolism suggests agonists of the adenosine A2A receptor (ADORA2A) can trigger regeneration of pancreatic b cells and thus could help treat diabetes.

ADORA2A plays a central role in adenosine metabolism and signaling.

Breakdown of adenosine by adenosine kinase (AK) and adenosine deaminase (ADA) generates essential metabolic molecules, including inosine, AMP and ATP [a]. When ATP is released into the extracellular space, it can be converted back to adenosine, which binds and activates ADORA2A on the surface of neighboring cells [b]. ADORA2A then triggers downstream signaling via G proteins and kinases, such as adenylate cyclase and phosphoinositide 3-kinase (PI3K) [c], which finally leads to expression of multiple genes involved in b cell regeneration, inflammation and vasodilation [d].

The UCSF group used a zebrafish screen to identify small molecules that acted on the adenosine pathway. The most potent compound, 5ʹ-N-ethylcarboxamidoadenosine (NECA), agonized ADORA2A and increased b cell proliferation in zebrafish and diabetic mice.