alpha2A-adrenergic receptors in the genetics, pathogenesis, and treatment of type 2 diabetes.
Insulin secretion from pancreatic islets is inhibited by the activation of beta cell alpha(2A)-adrenergic receptors (alpha(2A)ARs). Increased expression of alpha(2A)ARs, then, would depress insulin release, which is a pathogenic mechanism of type 2 diabetes. Using congenic rats derived from an inbred model of type 2 diabetes, Rosengren et al. showed that a chromosomal region that includes the gene encoding alpha(2A)AR, Adra2a, is associated with increased messenger RNA and protein expression and decreased insulin release. A single-nucleotide polymorphism in the human ADRA2A gene was associated with decreased insulin secretion in normal people during glucose challenge and was also associated with type 2 diabetes. These findings offer another genetic association locus for the disease, with concordant biochemical and expression phenotypes, and also provide a potential new pathway for therapeutic intervention.
Liggett
Stephen B
SB
University of Maryland School of Medicine, Baltimore, MD 21201, USA. sligg001@umaryland.edu.
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
C547768:ADRA2A protein, human; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007004:Hypoglycemic Agents; D007328:Insulin; D018341:Receptors, Adrenergic, alpha-2