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Diabetologia

Erschienen in:

01.02.2007 | Article

Role of inflammatory mediators in the suppression of insulin receptor phosphorylation in circulating mononuclear cells of obese subjects

verfasst von: H. Ghanim, A. Aljada, N. Daoud, R. Deopurkar, A. Chaudhuri, P. Dandona

Erschienen in: Diabetologia | Ausgabe 2/2007

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Abstract

Aims/hypothesis

Obesity is associated with insulin resistance and inflammation. The circulating human mononuclear cell (MNC) has been shown to respond to low-dose insulin infusion. We have now investigated whether in obesity: (1) phosphorylated insulin receptor beta subunit (p-INSR-β) is reduced in the MNC; (2) pro-inflammatory mediators including inhibitor of kappa light polypeptide gene enhancer in B cells-kinase beta (IKBKB), suppressor of cytokine signalling-3 (SOCS) and protein kinase C-beta 2 (PRKCB2) are increased and related to p-INSR-β; and (3) the reduction in MNC p-INSR-β is related to the reduction in insulin sensitivity.

Materials and methods

MNCs were prepared from fasting blood samples of 16 normal weight and 16 obese female subjects.

Results

Our data show that p-INSR-β is reduced significantly in MNCs from obese subjects compared with that of normal controls. MNCs from obese subjects have higher IKBKB expression, increased nuclear factor kappa B (NFκB) binding and higher mRNA expression of TNFAIP1 and IL6 genes. NFκB binding, TNFAIP1 mRNA and plasma C-reactive protein are inversely related to p-INSR-β. PRKCB2 mRNA and protein expression were significantly higher in the obese subjects and were related significantly to pro-inflammatory mediators but not to p-INSR-β. SOCS3 mRNA expression was markedly elevated and positively related to pro-inflammatory mediators including IKBKB and PRKCB2 on the one hand and inversely related to p-INSR-β on the other.

Conclusions/interpretation

We conclude that in obesity the MNC is characterised by reduced p-INSR-β and increased inflammatory mediators including IKBKB, PRKCB2 and SOCS3. The increase in SOCS3 but not IKBKB or PRKCB2 is related inversely to p-INSR-β and might mediate the inhibition of p-INSR-β. These data elucidate the relationship between inflammation and insulin resistance using the MNC as a model.

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Titel: Role of inflammatory mediators in the suppression of insulin receptor phosphorylation in circulating mononuclear cells of obese subjects
verfasst von: H. Ghanim
A. Aljada
N. Daoud
R. Deopurkar
A. Chaudhuri
P. Dandona
Publikationsdatum: 01.02.2007
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 2/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-006-0508-9

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Role of inflammatory mediators in the suppression of insulin receptor phosphorylation in circulating mononuclear cells of obese subjects

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