The Arg64 β3-adrenergic receptor (β3AR) variant is associated with an earlier age of onset of diabetes mellitus. The aims of this study were: i) to characterize the insulin secretory activity of human subjects carrying the Arg64 allele; ii) to investigate whether β3AR is expressed by islet cells; iii) to study whether cell transfection of islet-derived β-cells with the β3AR Arg64 variant was capable of altering the insulin secretory activity of cells. We observed a lower level of insulin secretion in response to an i.v. glucose tolerance test in individuals carrying the Arg64 polymorphism compared to wild-type controls. Western blotting of human pancreas demonstrated that the β3AR gene is transcribed and translated in the human pancreas; and immunostaining showed that it is expressed by the islets of Langerhans. Transfection of cultured rat βcells with the wild-type human β3AR produced a ligand-dependent insulin secretion. Cell transfection with the Arg64 variant induced a downregulation of insulin secretion, both spontaneously and after exposure to a human β3AR agonist. Furthermore, while transfection with the wild-type β3AR preserved the glucosedependent secretion of insulin, expression of the variant receptor rendered the host cells significantly less responsive to glucose.
|Original language||English (US)|
|Number of pages||11|
|Journal||Journal of Endocrine Genetics|
|State||Published - Dec 1 2002|
- Diabetes mellitus
- β-adrenergic receptor
ASJC Scopus subject areas