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

Diabetologia. 2007 Feb;50(2):278-85. doi: 10.1007/s00125-006-0508-9. Epub 2006 Dec 16.


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-beta) 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-beta; and (3) the reduction in MNC p-INSR-beta 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-beta 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 (NFkappaB) binding and higher mRNA expression of TNFAIP1 and IL6 genes. NFkappaB binding, TNFAIP1 mRNA and plasma C-reactive protein are inversely related to p-INSR-beta. 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-beta. 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-beta on the other.

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

MeSH terms

  • Adult
  • Blood Pressure
  • Cholesterol / blood
  • Fatty Acids, Nonesterified / blood
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / physiopathology*
  • Insulin / blood
  • Leukocytes, Mononuclear / physiology*
  • Middle Aged
  • Obesity / blood*
  • Obesity / physiopathology
  • Phosphorylation
  • Receptor, Insulin / blood*
  • Reference Values
  • Triglycerides / blood


  • Fatty Acids, Nonesterified
  • Insulin
  • Triglycerides
  • Cholesterol
  • Receptor, Insulin