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Sökning: onr:"swepub:oai:lup.lub.lu.se:7fd9ac83-e63e-44f4-8296-45cf506939e8" > Dissociation betwee...

Dissociation between Skeletal Muscle Inhibitor-{kappa}B Kinase/Nuclear Factor-{kappa}B Pathway Activity and Insulin Sensitivity in Nondiabetic Twins.

Friedrichsen, Martin (författare)
Ribel-Madsen, Rasmus (författare)
Wojtaszewski, Jørgen (författare)
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Grunnet, Louise (författare)
Richter, Erik A (författare)
Billestrup, Nils (författare)
Ploug, Thorkil (författare)
Vaag, Allan (författare)
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
Poulsen, Pernille (författare)
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 (creator_code:org_t)
Oxford University Press, 2010
2010
Engelska.
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 1945-7197. ; 95:1, s. 414-421
  • Tidskriftsartikel (refereegranskat)
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)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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