ZFIN ID: ZDB-PUB-120529-1
Adenosine Signaling Promotes Regeneration of Pancreatic beta Cells In Vivo
Andersson, O., Adams, B.A., Yoo, D., Ellis, G.C., Gut, P., Anderson, R.M., German, M.S., and Stainier, D.Y.
Date: 2012
Source: Cell Metabolism   15(6): 885-894 (Journal)
Registered Authors: Anderson, Ryan, Ellis, Greg, Gut, Philipp, Stainier, Didier, Yoo, Daniel
Keywords: none
MeSH Terms:
  • Adenosine/metabolism
  • Adenosine/physiology*
  • Adenosine-5'-(N-ethylcarboxamide)/pharmacology*
  • Adenosine-5'-(N-ethylcarboxamide)/therapeutic use
  • Animals
  • Blood Glucose
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Diabetes Mellitus, Experimental/drug therapy
  • Diabetes Mellitus, Experimental/pathology
  • Drug Evaluation, Preclinical
  • Insulin-Secreting Cells/drug effects
  • Insulin-Secreting Cells/metabolism*
  • Insulin-Secreting Cells/physiology
  • Larva/drug effects
  • Mice
  • Pancreas/drug effects
  • Pancreas/pathology
  • Pancreas/physiology
  • Purinergic P1 Receptor Agonists/pharmacology*
  • Purinergic P1 Receptor Agonists/therapeutic use
  • Receptor, Adenosine A2A/metabolism
  • Regeneration
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed: 22608007 Full text @ Cell Metab.

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 52-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.