Intercellular Adhesion Molecule-1 Concentration Is Genetically Correlated With Insulin Resistance, Obesity, and HDL Concentration in Mexican Americans

Kent, Jack W.; Comuzzie, Anthony G.; Mahaney, Michael C.; Almasy, Laura; Rainwater, David L.; VandeBerg, John L.; MacCluer, Jean W.; Blangero, John

doi:10.2337/diabetes.53.10.2691

Cited by 58 publications

(50 citation statements)

References 27 publications

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“…Soluble forms of ICAM1 and VCAM1 have been found to enter the systemic circulation, as a result of proteolytic cleavage at the cell surface, releasing the extracellular domain. Indeed, sICAM1 and sVCAM1 levels are higher in insulin resistance, obesity and type 2 diabetes (Guler et al 2002, Leinonen et al 2003, Kent et al 2004. There is also evidence indicating that women with GDM develop endothelial dysfunction during pregnancy (Knock et al 1997), and despite returning to NGT, endothelial dysfunction is still evident in women 1-year post GDM pregnancy (Pleiner et al 2007).…”

Section: Figurementioning

confidence: 88%

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

Lappas¹

2014

Journal of Endocrinology

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Maternal peripheral insulin resistance and increased inflammation are two features of pregnancies, complicated by gestational diabetes mellitus (GDM). The nucleotide-binding oligomerisation domain (NOD) intracellular molecules recognise a wide range of microbial products, as well as other intracellular danger signals, thereby initiating inflammation through activation of nuclear factor kB (NFkB). The aim of this study was to determine whether levels of NOD1 and NOD2 are increased in adipose tissue of women with GDM. The effect of NOD1 and NOD2 activation on inflammation and the insulin signalling pathway was also assessed. NOD1, but not NOD2, expression was higher in omental and subcutaneous adipose tissues obtained from women with GDM when compared with those from women with normal glucose tolerance (NGT). In both omental and subcutaneous adipose tissues from NGTand GDM women, the NOD1 ligand g-D-glutamyl-meso-diaminopimelic acid (iE-DAP) significantly induced the expression and secretion of the pro-inflammatory cytokine interleukin 6 (IL6) and chemokine IL8; COX2 (PTGS2) gene expression and subsequent prostaglandin production; the expression and secretion of the extracellular matrix remodelling enzyme matrix metalloproteinase 9 (MMP9) and the gene expression and secretion of the adhesion molecules ICAM1 and VCAM1. There was no effect of the NOD2 ligand muramyl dipeptide on any of the endpoints tested. The effects of the NOD1 ligand iE-DAP were mediated via NFkB, as the NFkB inhibitor BAY 11-7082 significantly attenuated iE-DAP-induced expression and secretion of pro-inflammatory cytokines, COX2 gene expression and subsequent prostaglandin production, MMP9 expression and secretion and ICAM1 and VCAM1 gene expression and secretion. In conclusion, the present findings describe an important role for NOD1 in the development of insulin resistance and inflammation in pregnancies complicated by GDM.

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Section: Figurementioning

confidence: 88%

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

Lappas¹

2014

Journal of Endocrinology

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“…Inflammation of the vascular wall causes endothelial cells to express a wide variety of endothelial adhesion molecules, including intracellular adhesion molecule-1. sICAM-1 can be regarded as a marker of both endothelial function and inflammation (11) that is associated with atherosclerotic progression (44) and its levels are increased in obesity (9,(14)(15)(16)(17)19). It has been suggested that sICAM-1 mediated endothelial dysfunction is stimulated by cytokines secreted by adipose tissue (45).…”

Section: All Data Are Presented As the Mean ± S Bmi Body Mass Indexmentioning

confidence: 99%

“…Disturbed endothelial function can be assessed by measuring the level of these molecules. The concentration of soluble intracellular adhesion molecule-1 (sICAM1) and plasminogen activator inhibitor 1 (PAI-1) have been shown to be the earliest markers of endothelial dysfunction (6,7) and there is evidence that these substances are increased in obese patients (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Obesity, endothelial function and inflammation: the effects of weight loss after bariatric surgery

Gómez¹,

Ortega²,

Aragón‐Alonso³

et al. 2016

Nutr Hosp

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Palabras clave:Obesidad. Cirugía bariátrica. Infl amación. Función endotelial. Resistencia a la insulina. ResumenObjetivo: la obesidad está asociada con un aumento del riesgo de enfermedad cardiovascular. Se ha propuesto una relación causal entre obesidad, infl amación, resistencia a la insulina, y disfunción endotelial. El objetivo de este estudio fue valorar marcadores de insulinorresistencia, infl amación y disfunción endotelial en pacientes con obesidad mórbida antes y después de la pérdida de peso por cirugía bariátrica. Métodos: se midieron las concentraciones séricas de moléculas solubles de adhesión intercelular tipo 1 (sICAM-1), inhibidor del activador del plasminógeno tipo 1 (PAI-1), proteína C reactiva de alta sensibilidad (hs-PCR) e interleucina 6 (IL-6) en 79 pacientes con obesidad mórbida antes y a los 3, 6 y 12 meses de la realización de un by-pass gástrico. También se evaluaron índices de resistencia a la insulina. Resultados: a los 12 meses de la cirugía disminuyeron los niveles de sICAM1 (p < 0,001), PAI-1 (p < 0,05), hs-CRP (p < 0,001), IL-6 (p < 0,001) y el índice homeostasis model assessment (HOMA) (p < 0,001) y aumentó el índice McAuley (p < 0,001). Los niveles basales de hs-PCR estaban correlacionados con los de sICAM-1 (r = 0,450, p < 0,01) y de IL-6 (r = 0,451, p < 0,01). También existía correlación entre el descenso de los niveles de PAI-1 y el descenso de hs-PCR (r = 0,425, p < 0,01) y triglicéridos (r = 0,351, p < 0,01). Conclusiones: en pacientes con obesidad mórbida una importante pérdida de peso por cirugía bariátrica se acompaña de una mejora signifi cativa de marcadores infl amatorios, de función endotelial e insulinorresistencia, lo que puede suponer una disminución del riesgo cardiovascular. Existe una relación entre mejora del perfi l infl amatorio y función endotelial. AbstractObjective: Obesity is associated with a high risk for atherosclerotic cardiovascular disease. There is a causal association between obesity, infl ammation, insulin resistance (IR) and endothelial dysfunction. The aim of this study was to evaluate changes in IR, proinfl ammatory state and markers of endothelial dysfunction in morbidly obese patients after weight loss following bariatric surgery. Methods: In this study, we measured the levels of soluble intracellular adhesion molecule-1 (sICAM1), plasminogen activator inhibitor 1 (PAI-1), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) in 79 morbidly obese patients at baseline and 3, 6 and 12 months after gastric bypass. Also, we evaluated changes in IR. Results: Twelve months after surgery, there was a signifi cant decrease in plasma levels of sICAM1 (p < 0.001), PAI-1 (p < 0.05), hs-CRP (p < 0.001), IL-6 (p < 0.001) and homeostasis model assessment (HOMA) (p < 0.001) and a signifi cant increase of McAuley index (McAuley) (p < 0.001). Baseline levels of hs-PCR were positively correlated with sICAM-1 (r = 0.450, p < 0.01) and IL-6 (r = 0.451, p < 0.01). Signifi cant correlations were also found between the decrease of PAI-1 and the ...

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“…Polymorphisms in human UBL5 are associated with variation in body composition; blood levels of total cholesterol, LDL, and triglycerides; and insulin response to glucose challenge [23]. Given the correlation between inflammation and the metabolic syndrome [6,9] it is interesting to note that the Chr. 19 QTL coincides with genes related to dyslipidemia, hypertension, and insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study [9] we found that sICAM-1 levels are genetically correlated with several measures of obesity and insulin resistance in a Mexican American population with elevated prevalence of obesity and T2DM: the San Antonio Family Heart Study (SAFHS, [10]). This finding provides suggestive evidence for the existence of common genetic factors underlying development of obesity, T2DM, and inflammatory disease.…”

Section: Introductionmentioning

confidence: 99%

Quantitative trait locus on Chromosome 19 for circulating levels of intercellular adhesion molecule-1 in Mexican Americans

et al. 2007

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Circulating soluble intercellular adhesion molecule-1 (sICAM-1) is a biochemical marker of inflammation. We performed variance-components-based quantitative genetic analyses in SOLAR of sICAM-1 in 1170 individuals from Mexican American families in the San Antonio Family Heart Study. The trait is heritable (h 2 = 0.50±0.06, P<10 -6 ). Multipoint linkage analysis using a ∼10-cM microsatellite map revealed a region on Chromosome 19p near marker D19S586 showing strong evidence of linkage for sICAM-1 (empirically adjusted univariate-equivalent LOD = 4.95), coincident with the structural gene ICAM1. This region has been identified previously as a QTL for inflammatory, autoimmune, and metabolic syndrome traits. There is significant evidence (P=0.0023) of locus heterogeneity for sICAM-1 in this sample: a subset of pedigrees contributes most of the linkage signal for sICAM-1 on Chromosome 19, suggesting a logical focus for future genetic dissection of the trait.

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Intercellular Adhesion Molecule-1 Concentration Is Genetically Correlated With Insulin Resistance, Obesity, and HDL Concentration in Mexican Americans

Cited by 58 publications

References 27 publications

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

Obesity, endothelial function and inflammation: the effects of weight loss after bariatric surgery

Quantitative trait locus on Chromosome 19 for circulating levels of intercellular adhesion molecule-1 in Mexican Americans

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