Inheritance of the Arg64 polymorphic variants of the β3-adrenergic receptor is linked to impaired insulin secretion

Hongxiang Hui, Jeremy D. Walston, Riccardo Perfetti

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)63-73
Number of pages11
JournalJournal of Endocrine Genetics
Volume3
Issue number2
StatePublished - Dec 1 2002

Keywords

  • Beta-cells
  • Diabetes mellitus
  • Insulin
  • β-adrenergic receptor

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Genetics(clinical)

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