Trp64Arg variant of the β3-adrenoceptor and insulin resistance in obese postmenopausal women

Ernesto García-Rubi, Raymond D. Starling, André Tchernof, Dwight E. Matthews, Jeremy D. Walston, Alan R. Shuldiner, Kristi Silver, Eric T. Poehlman, Jorge Calles-Escandón

Research output: Contribution to journalArticle

Abstract

There is controversy regarding the role of the Trp64Arg variant of the β3-adrenergic receptor (β3AR) gene in the pathogenesis of insulin resistance. The modest effect of the variant as well as differences in study design, gender, age, and genetic background may contribute to divergent results among investigations. Insulin sensitivity (euglycemic clamp and tracers) was measured in 13 obese women (57 ± 6 yr old) heterozygous for the β3AR variant and in 14 women (57 ± 4 yr old) homozygous for the normal gene. Groups were matched for age, body composition, intraabdominal fat, sc abdominal fat, physical activity level, and aerobic capacity. Exogenous glucose infusion during the clamp was significantly lower (P = 0.03) in β3AR heterozygotes (241 ± 135 mg/min) vs. normal homozygotes (379 ± 172 mg/min). Basal endogenous glucose production was not different (P = 0.20) between heterozygotes (175 ± 27 mg/min) and normal homozygotes (164 ± 14 mg/min). Endogenous glucose production during hyperinsulinemia was also not different (P = 0.22) between heterozygotes (77 ± 57 mg/min) and normal homozygotes (56 ± 16 mg/min). Total glucose disposal adjusted for residual endogenous glucose production was lower (P = 0.049) for heterozygotes (320 ± 111 mg/min) than for normal homozygotes (441 ± 183 mg/min). Our results suggest that obese postmenopausal women who are heterozygous for the Trp64Arg variant in the β3AR gene have greater insulin resistance than age-, body composition-, and physical activity-matched women homozygous for the normal gene.

Original languageEnglish (US)
Pages (from-to)4002-4005
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number11
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Fingerprint Dive into the research topics of 'Trp<sup>64</sup>Arg variant of the β<sub>3</sub>-adrenoceptor and insulin resistance in obese postmenopausal women'. Together they form a unique fingerprint.

  • Cite this

    García-Rubi, E., Starling, R. D., Tchernof, A., Matthews, D. E., Walston, J. D., Shuldiner, A. R., Silver, K., Poehlman, E. T., & Calles-Escandón, J. (1998). Trp64Arg variant of the β3-adrenoceptor and insulin resistance in obese postmenopausal women. Journal of Clinical Endocrinology and Metabolism, 83(11), 4002-4005. https://doi.org/10.1210/jcem.83.11.5225