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Dissociation betwee...
Dissociation between Skeletal Muscle Inhibitor-{kappa}B Kinase/Nuclear Factor-{kappa}B Pathway Activity and Insulin Sensitivity in Nondiabetic Twins.
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Friedrichsen, Martin (författare)
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Ribel-Madsen, Rasmus (författare)
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Wojtaszewski, Jørgen (författare)
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Grunnet, Louise (författare)
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Richter, Erik A (författare)
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Billestrup, Nils (författare)
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Ploug, Thorkil (författare)
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- Vaag, Allan (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Poulsen, Pernille (författare)
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(creator_code:org_t)
- The Endocrine Society, 2010
- 2010
- Engelska.
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95:1, s. 414-421
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://academic.oup...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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