Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Overexpression of alpha2A-adrenergic receptors contributes to type 2 diabetes.

Authors: Rosengren, AH  Jokubka, R  Tojjar, D  Granhall, C  Hansson, O  Li, DQ  Nagaraj, V  Reinbothe, TM  Tuncel, J  Eliasson, L  Groop, L  Rorsman, P  Salehi, A  Lyssenko, V  Luthman, H  Renstrom, E 
Citation: Rosengren AH, etal., Science. 2010 Jan 8;327(5962):217-20. Epub 2009 Nov 19.
Pubmed: (View Article at PubMed) PMID:19965390
DOI: Full-text: DOI:10.1126/science.1176827

Several common genetic variations have been associated with type 2 diabetes, but the exact disease mechanisms are still poorly elucidated. Using congenic strains from the diabetic Goto-Kakizaki rat, we identified a 1.4-megabase genomic locus that was linked to impaired insulin granule docking at the plasma membrane and reduced beta cell exocytosis. In this locus, Adra2a, encoding the alpha2A-adrenergic receptor [alpha(2A)AR], was significantly overexpressed. Alpha(2A)AR mediates adrenergic suppression of insulin secretion. Pharmacological receptor antagonism, silencing of receptor expression, or blockade of downstream effectors rescued insulin secretion in congenic islets. Furthermore, we identified a single-nucleotide polymorphism in the human ADRA2A gene for which risk allele carriers exhibited overexpression of alpha(2A)AR, reduced insulin secretion, and increased type 2 diabetes risk. Human pancreatic islets from risk allele carriers exhibited reduced granule docking and secreted less insulin in response to glucose; both effects were counteracted by pharmacological alpha(2A)AR antagonists.


Disease Annotations
Gene Ontology Annotations
Phenotype Annotations
Objects Annotated
Objects referenced in this article

Additional Information

CRRD Object Information
CRRD ID: 2316628
Created: 2010-02-18
Species: All species
Last Modified: 2010-02-18
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.