Dissociation between skeletal muscle inhibitor-{kappa}B kinase/nuclear factor-{kappa}B pathway activity and insulin sensitivity in nondiabetic twins

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Standard

Dissociation between skeletal muscle inhibitor-{kappa}B kinase/nuclear factor-{kappa}B pathway activity and insulin sensitivity in nondiabetic twins. / Friedrichsen, Martin; Ribel-Madsen, Rasmus; Wojtaszewski, Jørgen; Grunnet, Louise; Richter, Erik A.; Billestrup, Nils; Ploug, Thorkil; Vaag, Allan; Poulsen, Pernille.

I: Journal of Clinical Endocrinology and Metabolism, Bind 95, Nr. 1, 2010, s. 414-421.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Friedrichsen, M, Ribel-Madsen, R, Wojtaszewski, J, Grunnet, L, Richter, EA, Billestrup, N, Ploug, T, Vaag, A & Poulsen, P 2010, 'Dissociation between skeletal muscle inhibitor-{kappa}B kinase/nuclear factor-{kappa}B pathway activity and insulin sensitivity in nondiabetic twins', Journal of Clinical Endocrinology and Metabolism, bind 95, nr. 1, s. 414-421. https://doi.org/10.1210/jc.2009-1147

APA

Friedrichsen, M., Ribel-Madsen, R., Wojtaszewski, J., Grunnet, L., Richter, E. A., Billestrup, N., Ploug, T., Vaag, A., & Poulsen, P. (2010). Dissociation between skeletal muscle inhibitor-{kappa}B kinase/nuclear factor-{kappa}B pathway activity and insulin sensitivity in nondiabetic twins. Journal of Clinical Endocrinology and Metabolism, 95(1), 414-421. https://doi.org/10.1210/jc.2009-1147

Vancouver

Friedrichsen M, Ribel-Madsen R, Wojtaszewski J, Grunnet L, Richter EA, Billestrup N o.a. Dissociation between skeletal muscle inhibitor-{kappa}B kinase/nuclear factor-{kappa}B pathway activity and insulin sensitivity in nondiabetic twins. Journal of Clinical Endocrinology and Metabolism. 2010;95(1):414-421. https://doi.org/10.1210/jc.2009-1147

Author

Friedrichsen, Martin ; Ribel-Madsen, Rasmus ; Wojtaszewski, Jørgen ; Grunnet, Louise ; Richter, Erik A. ; Billestrup, Nils ; Ploug, Thorkil ; Vaag, Allan ; Poulsen, Pernille. / Dissociation between skeletal muscle inhibitor-{kappa}B kinase/nuclear factor-{kappa}B pathway activity and insulin sensitivity in nondiabetic twins. I: Journal of Clinical Endocrinology and Metabolism. 2010 ; Bind 95, Nr. 1. s. 414-421.

Bibtex

@article{24ae4760d06111dea1f3000ea68e967b,
title = "Dissociation between skeletal muscle inhibitor-{kappa}B kinase/nuclear factor-{kappa}B pathway activity and insulin sensitivity in nondiabetic twins",
abstract = "Context: Several studies suggest a link between increased activity of the inflammatory inhibitor-kappaB kinase/nuclear factor-kappaB (IKK/NF-kappaB) pathway in skeletal muscle and insulin resistance. Objective: We aimed to study the regulation of skeletal muscle IKK/NF-kappaB pathway activity as well as the association with glucose metabolism and skeletal muscle insulin signaling. Methods: The study population included a metabolically well-characterized cohort of young and elderly predominantly nondiabetic twins (n = 181). Inhibitor-kappaBbeta (IkappaBbeta) protein levels are negatively associated with IKK/NF-kappaB pathway activity and were used to evaluate pathway activity with p65 levels included as loading control. This indirect measure for IKK/NF-kappaB pathway activity was validated by a p65 binding assay. Results: Evaluating the effects of heritability, age, sex, obesity, aerobic capacity, and several hormonal factors (eg insulin and TNF-alpha), only sex and age were significant predictors of IkappaBbeta to p65 ratio (28% decreased ratio in the elderly, P < 0.01, and 49% increased in males P < 0.01). IkappaBbeta to p65 ratio was unrelated to peripheral insulin sensitivity (P = 0.51) and in accordance with this also unrelated to proximal insulin signaling (P = 0.81). Although no association was seen with plasma glucose after oral glucose challenge, there was a tendency for lower IkappaBbeta to p65 ratio (adjusted for age and sex) in subjects with impaired as opposed to normal glucose tolerance (P = 0.055). Conclusions: Altogether the subtle elevated IKK/NF-kappaB pathway activity seen in glucose-intolerant subjects suggests that IKK/NF-kappaB pathway activation may be secondary to impaired glucose tolerance and that skeletal muscle IKK/NF-kappaB pathway activity is unlikely to play any major role in the control of skeletal muscle insulin action in nondiabetic subjects.",
author = "Martin Friedrichsen and Rasmus Ribel-Madsen and J{\o}rgen Wojtaszewski and Louise Grunnet and Richter, {Erik A.} and Nils Billestrup and Thorkil Ploug and Allan Vaag and Pernille Poulsen",
note = "CURIS 2010 5200 002",
year = "2010",
doi = "10.1210/jc.2009-1147",
language = "English",
volume = "95",
pages = "414--421",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "1",

}

RIS

TY - JOUR

T1 - Dissociation between skeletal muscle inhibitor-{kappa}B kinase/nuclear factor-{kappa}B pathway activity and insulin sensitivity in nondiabetic twins

AU - Friedrichsen, Martin

AU - Ribel-Madsen, Rasmus

AU - Wojtaszewski, Jørgen

AU - Grunnet, Louise

AU - Richter, Erik A.

AU - Billestrup, Nils

AU - Ploug, Thorkil

AU - Vaag, Allan

AU - Poulsen, Pernille

N1 - CURIS 2010 5200 002

PY - 2010

Y1 - 2010

N2 - Context: Several studies suggest a link between increased activity of the inflammatory inhibitor-kappaB kinase/nuclear factor-kappaB (IKK/NF-kappaB) pathway in skeletal muscle and insulin resistance. Objective: We aimed to study the regulation of skeletal muscle IKK/NF-kappaB pathway activity as well as the association with glucose metabolism and skeletal muscle insulin signaling. Methods: The study population included a metabolically well-characterized cohort of young and elderly predominantly nondiabetic twins (n = 181). Inhibitor-kappaBbeta (IkappaBbeta) protein levels are negatively associated with IKK/NF-kappaB pathway activity and were used to evaluate pathway activity with p65 levels included as loading control. This indirect measure for IKK/NF-kappaB pathway activity was validated by a p65 binding assay. Results: Evaluating the effects of heritability, age, sex, obesity, aerobic capacity, and several hormonal factors (eg insulin and TNF-alpha), only sex and age were significant predictors of IkappaBbeta to p65 ratio (28% decreased ratio in the elderly, P < 0.01, and 49% increased in males P < 0.01). IkappaBbeta to p65 ratio was unrelated to peripheral insulin sensitivity (P = 0.51) and in accordance with this also unrelated to proximal insulin signaling (P = 0.81). Although no association was seen with plasma glucose after oral glucose challenge, there was a tendency for lower IkappaBbeta to p65 ratio (adjusted for age and sex) in subjects with impaired as opposed to normal glucose tolerance (P = 0.055). Conclusions: Altogether the subtle elevated IKK/NF-kappaB pathway activity seen in glucose-intolerant subjects suggests that IKK/NF-kappaB pathway activation may be secondary to impaired glucose tolerance and that skeletal muscle IKK/NF-kappaB pathway activity is unlikely to play any major role in the control of skeletal muscle insulin action in nondiabetic subjects.

AB - Context: Several studies suggest a link between increased activity of the inflammatory inhibitor-kappaB kinase/nuclear factor-kappaB (IKK/NF-kappaB) pathway in skeletal muscle and insulin resistance. Objective: We aimed to study the regulation of skeletal muscle IKK/NF-kappaB pathway activity as well as the association with glucose metabolism and skeletal muscle insulin signaling. Methods: The study population included a metabolically well-characterized cohort of young and elderly predominantly nondiabetic twins (n = 181). Inhibitor-kappaBbeta (IkappaBbeta) protein levels are negatively associated with IKK/NF-kappaB pathway activity and were used to evaluate pathway activity with p65 levels included as loading control. This indirect measure for IKK/NF-kappaB pathway activity was validated by a p65 binding assay. Results: Evaluating the effects of heritability, age, sex, obesity, aerobic capacity, and several hormonal factors (eg insulin and TNF-alpha), only sex and age were significant predictors of IkappaBbeta to p65 ratio (28% decreased ratio in the elderly, P < 0.01, and 49% increased in males P < 0.01). IkappaBbeta to p65 ratio was unrelated to peripheral insulin sensitivity (P = 0.51) and in accordance with this also unrelated to proximal insulin signaling (P = 0.81). Although no association was seen with plasma glucose after oral glucose challenge, there was a tendency for lower IkappaBbeta to p65 ratio (adjusted for age and sex) in subjects with impaired as opposed to normal glucose tolerance (P = 0.055). Conclusions: Altogether the subtle elevated IKK/NF-kappaB pathway activity seen in glucose-intolerant subjects suggests that IKK/NF-kappaB pathway activation may be secondary to impaired glucose tolerance and that skeletal muscle IKK/NF-kappaB pathway activity is unlikely to play any major role in the control of skeletal muscle insulin action in nondiabetic subjects.

U2 - 10.1210/jc.2009-1147

DO - 10.1210/jc.2009-1147

M3 - Journal article

C2 - 19875481

VL - 95

SP - 414

EP - 421

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -

ID: 15791244