Abstract
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) |
---|---|
Pages (from-to) | 63-73 |
Number of pages | 11 |
Journal | Journal of Endocrine Genetics |
Volume | 3 |
Issue number | 2 |
State | Published - Dec 1 2002 |
Keywords
- Beta-cells
- Diabetes mellitus
- Insulin
- β-adrenergic receptor
ASJC Scopus subject areas
- Genetics
- Endocrinology
- Genetics(clinical)