PUBLICATION

Adenosine Signaling Promotes Regeneration of Pancreatic beta Cells In Vivo

Authors
Andersson, O., Adams, B.A., Yoo, D., Ellis, G.C., Gut, P., Anderson, R.M., German, M.S., and Stainier, D.Y.
ID
ZDB-PUB-120529-1
Date
2012
Source
Cell Metabolism   15(6): 885-894 (Journal)
Registered Authors
Anderson, Ryan, Andersson, Olov, 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.
Abstract

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.

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