alpha2A-adrenergic receptors in the genetics, pathogenesis, and treatment of type 2 diabetes.

Abstract

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.