Table 7.

Selected IR-associated genes with DMS

Gene	Expression and CpG-methylation in SAT: observations from the current study	Previously reported findings of gene/protein function
GAB1	SAT CpG methylation in the gene body was inversely associated with gene expression and IR was associated with lower GAB1 expression (fold change IR vs IS: 0.89)	GAB1 is an adaptor molecule that can stimulate adipocyte glucose uptake through a GAB1/PI 3-kinase/PKB/AS160 pathway [31]
PFKFB3	SAT CpG methylation in the promoter was directly associated with gene expression, whilst CpG methylation in the gene body was inversely associated. IR was associated with lower PFKFB3 expression (fold change IR vs IS: 0.80)	PFKFB3 regulates the steady-state concentration of fructose-2,6-bisphosphate, a potent activator of a key regulatory enzyme of glycolysis. Fat cell overexpression of PFKFB3 enhances insulin sensitivity [32]
IRS2	SAT CpG methylation in the 5′ region was inversely associated with gene expression and IR was associated with lower IRS2 expression (fold change IR vs IS: 0.85)	IRS2 mediates the effects of insulin on glucose homeostasis and cell growth
PTPRJ	SAT CpG methylation in the gene body was inversely associated with gene expression and IR was associated with higher PTPRJ expression (fold change IR vs IS: 1.18)	Recently it was shown that high-fat diet fed Ptprj −/− mice displayed enhanced insulin sensitivity and improved glucose tolerance, thus establishing PTPRJ as a negative regulator of insulin signalling [33]

AS160, Akt substrate 160-KD; GAB1, growth factor receptor bound protein 2-associated binding protein 1; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3; PI 3-kinase, phosphatidylinositol 3-kinase; PKB, protein kinase B; PTPRJ, protein-tyrosine phosphatases, receptor-type, J