Abstract: Objective To 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. Methods Forty 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. Results In the fasting and feeding hyperhomocysteimia 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 hyperhomocysteimia groups, but Akt mRNA and protein expressions were
comparable with those in the control groups. Conclusion Homocysteine lowers the uptake and utilization of glucose by
down-regulating PDK1 expression and affecting PI3K/Akt signal pathway to cause disturbance of glucose metabolism.