OBJECTIVETo study the effect of homcysteine on the expression of 3-phosphoinositide-dependent protein kinase 1 (PDK1) in the adipose tissue and explore whether PDK1 inhibits p-Akt(Thr-308) expression and affect PI3K/Akt signal pathway to decrease glucose uptake and utilization.

METHODSForty mice were randomly divided into 4 groups (n=10), namely the fasting control group, feeding control group, fasting hyperhomocysteinemia group, and feeding hyperhomocysteinemia group. In the two hyperhomocysteinemia groups, the mice were given water containing 1.5% methionine to induce hyperhomocysteinemia. Blood glucose and insulin levels in each group were determined, and the expressions of PDK1 and Akt mRNA in the adipose tissue were detected using RT-PCR; the expressions of PDK1, p-Akt(Thr-308) and Akt proteins were detected using Western blotting.

RESULTSIn the fasting and feeding hyperhomocysteinemia groups, blood glucose and insulin levels were significantly higher than those in the two control groups. The expressions of PDK1 mRNA and PDK1 and p-Akt(Thr-308) proteins were reduced in the two hyperhomocysteinemia groups, but Akt mRNA and protein expressions were comparable with those in the control groups.

CONCLUSIONHomocysteine lowers the uptake and utilization of glucose by down-regulating PDK1 expression and affecting PI3K/Akt signal pathway to cause disturbance of glucose metabolism.