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  • Energy expenditure, body composition and insulin response to glucose in male twins discordant for the Trp64Arg polymorphism of the beta3-adrenergic receptor gene. 16634992

    AIM: The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the beta3-adrenergic receptor (beta3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin secretion could play a role. METHODS: In 10 male twin pairs discordant for the Trp64Arg polymorphism, we examined insulin response to glucose by an oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), body composition by the bioimpedance method, dual-energy X-ray absorptiometry scanning and energy expenditure by indirect and direct calorimetry. RESULTS: Twins heterozygous for the Trp64Arg polymorphism showed significantly lower fat mass independent of the method used, and significantly lower fasting insulin and glucose concentrations compared with their homozygous wild-type co-twins. Correspondingly, insulin resistance and insulin secretion determined by homeostasis model assessment were significantly lower in twins carrying the Trp64Arg polymorphism. However, there were no significant differences in adiponectin levels, insulinogenic index assessed by OGTT, or insulin sensitivity, acute insulin response to glucose, glucose effectiveness or insulin disposition index assessed by minimal modelling of the FSIGT. Furthermore, there were no differences in sleeping, resting or post-prandial energy expenditure. CONCLUSIONS: In male twins with a high similarity in genetic and environmental background, the Trp64Arg polymorphism of the beta3AR gene is associated with lower fat mass, fasting insulin levels and an appropriate insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes.
    문서 타입:
    Reference
    카탈로그 번호:
    HL-81K
    제품명:
    Human Leptin RIA

  • Differences in circulating concentrations of total, free and bound leptin relate to gender and body composition in adult humans. 11026527

    We describe a radioimmunoassay (RIA) for total leptin and a gel filtration procedure for the separation of free and bound leptin in human serum. The RIA, based on a locally prepared antibody, has a minimum detection limit of 0.9 ng/mL, a working range (CV 10%) of 2.5-50 ng/mL, inter-assay precision of 10.2, 7.2 and 8.9%CV at 7.9, 15.4 and 30.0 ng/mL, respectively, 94% recovery of exogenous leptin (range 81.1-120.6%), exhibited parallelism and demonstrated no significant cross-reactivity or interferences. A difference plot of results from this method and those from a commercially available kit (Linco Research) demonstrated satisfactory agreement up to concentrations of 50 ng/mL total leptin, with no significant bias. A gender-dependent correlation was obtained between body mass index (BMI) and total leptin (r = 0.91, P0.001, n = 75 for men; r = 0.79, P0.001, n = 72 for women), with women having higher leptin concentrations than men for any given BMI. Gel filtration studies (inter-assay precision: 4.7%CV, n = 18) demonstrated that a variable fraction (between 10% and 40%) of total leptin in serum was bound with high affinity (Keq = 1.0-1.45 x 10(9) L/mol) to a non-albumin, non-lipid macromolecule. Binding affinities were found to be similar irrespective of gender or fat mass. A significant positive correlation between free or bound leptin concentrations and BMI was obtained for both men and women (r = 0.87-0.94); free and bound leptin concentrations were also significantly higher in women (P0.01) than in men for any given BMI, and higher in obese (P0.01) than in lean individuals. We conclude that leptin 'resistance' associated with obesity cannot be accounted for by reduced free leptin concentrations in serum and that the methods described are suitable for the investigation of total, free and bound leptin for both clinical and research purposes.
    문서 타입:
    Reference
    카탈로그 번호:
    HL-81K
    제품명:
    Human Leptin RIA
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