The glucose clamp reveals an association between adiponectin gene polymorphisms and insulin sensitivity in obese subjects

Abstract

Results concerning the association of adiponectin gene polymorphisms (single-nucleotide polymorphisms, SNPs) with obesity, type 2 diabetes (T2DM), metabolic disorders and insulin resistance have not lead to definite conclusions. The aim of our study was to investigate a possible association between the À11391G4A and À11377C4G SNPs of adiponectin gene and measure of insulin sensitivity evaluated by the hyperinsulinemic-euglycemic clamp in a group of 'uncomplicated' obese subjects (with no associated comorbidities) (n ¼ 99, mean age 35 years) with a history of obesity lasting at least 10 years. The study of uncomplicated obese subjects, free of possible confounding factors that could interfere with insulin sensitivity, such as pharmacological treatment, provides a good model to assess insulin sensitivity per se. We observed that subjects homozygous for the G allele at locus À11391 had lower M (mg/kg min)/fat-free mass (FFM) index and adiponectin levels compared to subjects with GA þ AA genotypes (P ¼ 0.002 and P ¼ 0.03, respectively) and subjects carrying the À11377G variant had lower M (mg/kg min)/FFM index and adiponectin levels compared to noncarriers (P ¼ 0.003 and P ¼ 0.03, respectively). Our results imply that the two promoter SNPs, À11391G4A and À11377C4G, of the adiponectin gene are associated with a reduced insulin sensitivity evaluated by hyperinsulinemic-euglycemic clamp in obese subjects.

The association of SNPs in ADIPOQ, ADIPOR1, and ADIPOR2 with insulin sensitivity in a cohort of adolescents and their parents

“…Although several previous studies have examined the association of clamp-derived insulin sensitivity with SNPs in ADIPOQ (Buzzetti et al 2007; Salmenniemi et al 2005; Stumvoll et al 2002; Ukkola et al 2005; Vozarova de Courten et al 2005), only one previous study used tag SNPs (Vozarova de Courten et al 2005), so there is little overlap between the results of this study and previous studies in the literature. Only one of the suggestive ADIPOQ SNPs has been examined previously in relation to insulin sensitivity;rs266729 was found to be significantly (p < .05) associated with clamp-derived insulin sensitivity in obese Italians (Buzzetti et al 2007) but was not significantly associated with the same phenotype in Pima Indians (Vozarova de Courten et al 2005).…”

“…Additional studies have identified SNPs in two receptors for adiponectin (ADIPOR1 and ADIPOR2) that may also affect the activity of adiponectin (Damcott et al 2005; Stefan et al 2005). Few studies have examined the association of SNPs in these genes with the moderately heritable (Rasmussen-Torvik et al 2007) gold standard measure of insulin sensitivity, the euglycemic clamp (Buzzetti et al 2007; Kantartzis et al 2006; Salmenniemi et al 2005; Stefan et al 2005; Ukkola et al 2005; Vozarova de Courten et al 2005) and only two other studies attempted to use tag SNPs to capture variation throughout the entire gene (Hara et al 2005; Vozarova de Courten et al 2005). Additionally, most previous studies have been conducted in middle-aged or older populations.…”

CB1R antagonist increases hepatic insulin clearance in fat-fed dogs likely via upregulation of liver adiponectin receptors

“…Adiponectin is produced in adipose tissues and released into the circulation and is directly linked to insulin sensitivity (22,47); specifically, euglycemic clamp studies performed in obese humans demonstrate that plasma adiponectin levels are significantly correlated with insulin sensitivity (7). In addition, RIM treatment has been shown to increase adiponectin mRNA expression in adipose tissue of obese fa/fa rats, diet-induced obese mice (18), and cultured adipocytes (2).…”

Asociación entre polimorfismos del gen de adiponectina y estado nutricional en escolares de la comuna de Hualpén

“…Nuestros resultados sugieren que dos variantes genéticas del gen de la adiponectina (+276GT y -11,377CG) potenciarían la reducción de la concentración sérica de adiponectina relacionada con el peso, aunque sin alcanzar significación estadística. El hecho de que otros autores hayan demostrado que las variantes +276GT y -11,377CG se asocian con una menor concentración sérica de adiponectina 17,20 podría atribuirse a un mayor tamaño muestral o una edad más avanzada de la muestra.…”

“…El polimorfismo +276GT (Intrón 2) se asocia con un aumento de los niveles de insulina plasmática, HOMA-IR y obesidad tanto en población adulta 11,13,16,17 como en población infantil 18 . El polimorfismo -11,377CG (Región promotora de AdipoQ) está asociado con aumento de la glicemia, insulinemia y disminución de la adiponectina plasmática en niños 14,17,19 y adultos 13,20,21 . El polimorfismo +45TG (Exón 2 de AdipoQ) se ha asociado con riesgo de insulino resistencia y obesidad en población adulta española, alemana, danesa y sueca 11,13,15,16,21 y en población infantil se ha relacionado con mayor nivel de glicemia, insulina, HOMA-IR (homeostatic model assessmentinsulin) e hipo-adiponectinemia 19 .…”