[HTML][HTML] Adenosine signaling promotes regeneration of pancreatic β cells in vivo

O Andersson, BA Adams, D Yoo, GC Ellis, P Gut… - Cell metabolism, 2012 - cell.com
Cell metabolism, 2012cell.com
Diabetes can be controlled with insulin injections, but a curative approach that restores the
number of insulin-producing β cells is still needed. Using a zebrafish model of diabetes, we
screened∼ 7,000 small molecules to identify enhancers of β cell regeneration. The
compounds we identified converge on the adenosine signaling pathway and include
exogenous agonists and compounds that inhibit degradation of endogenously produced
adenosine. The most potent enhancer of β cell regeneration was the adenosine agonist 5 …
Summary
Diabetes can be controlled with insulin injections, but a curative approach that restores the number of insulin-producing β cells is still needed. Using a zebrafish model of diabetes, we screened ∼7,000 small molecules to identify enhancers of β cell regeneration. The compounds we identified converge on the adenosine signaling pathway and include exogenous agonists and compounds that inhibit degradation of endogenously produced adenosine. The most potent enhancer of β cell regeneration was the adenosine agonist 5′-N-ethylcarboxamidoadenosine (NECA), which, acting through the adenosine receptor A2aa, increased β cell proliferation and accelerated restoration of normoglycemia in zebrafish. Despite markedly stimulating β cell proliferation during regeneration, NECA had only a modest effect during development. The proliferative and glucose-lowering effect of NECA was confirmed in diabetic mice, suggesting an evolutionarily conserved role for adenosine in β cell regeneration. With this whole-organism screen, we identified components of the adenosine pathway that could be therapeutically targeted for the treatment of diabetes.
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