Maternal peripheral insulin resistance and increased inflammation are two 
features of pregnancies, complicated by gestational diabetes mellitus (GDM). The 
nucleotide-binding oligomerisation domain (NOD) intracellular molecules 
recognise a wide range of microbial products, as well as other intracellular 
danger signals, thereby initiating inflammation through activation of nuclear 
factor κB (NFκB). The aim of this study was to determine whether levels of NOD1 
and NOD2 are increased in adipose tissue of women with GDM. The effect of NOD1 
and NOD2 activation on inflammation and the insulin signalling pathway was also 
assessed. NOD1, but not NOD2, expression was higher in omental and subcutaneous 
adipose tissues obtained from women with GDM when compared with those from women 
with normal glucose tolerance (NGT). In both omental and subcutaneous adipose 
tissues from NGT and GDM women, the NOD1 ligand g-d-glutamyl-meso-diaminopimelic 
acid (iE-DAP) significantly induced the expression and secretion of the 
pro-inflammatory cytokine interleukin 6 (IL6) and chemokine IL8; COX2 (PTGS2) 
gene expression and subsequent prostaglandin production; the expression and 
secretion of the extracellular matrix remodelling enzyme matrix 
metalloproteinase 9 (MMP9) and the gene expression and secretion of the adhesion 
molecules ICAM1 and VCAM1. There was no effect of the NOD2 ligand muramyl 
dipeptide on any of the endpoints tested. The effects of the NOD1 ligand iE-DAP 
were mediated via NFκB, as the NFκB inhibitor BAY 11-7082 significantly 
attenuated iE-DAP-induced expression and secretion of pro-inflammatory 
cytokines, COX2 gene expression and subsequent prostaglandin production, MMP9 
expression and secretion and ICAM1 and VCAM1 gene expression and secretion. In 
conclusion, the present findings describe an important role for NOD1 in the 
development of insulin resistance and inflammation in pregnancies complicated by 
GDM.