Abstract: Objective To investigate the expressions of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate
carboxykinase (PEPCK) in the liver of mice with hyperhomocysteinemia (HHcy) and explore the mechanism of
gluconeogenesis induced by homocysteine. Methods Fifty mice were randomly divided into normal control group (n=25) and
HHcy group (n=25) and fed with normal food and food supplemented with 1.5% methionine, respectively. After 3 months of
feeding, the fasting blood glucose and insulin levels were determined, and HOMA insulin resistance index (HOMA-IR) was
calculated. The expressions of G6Pase and PEPCK in the liver of mice were detected using RT-PCR and Western blotting.
Results The fasting blood glucose and insulin levels and HOMA-IR were significantly higher in HHcy group than in the
control group (P<0.05). RT-PCR and Western blotting showed that the hepatic expressions of G6Pase and PEPCK mRNA and
proteins increased significantly in HHcy group compared with those in the control group (P<0.05). Conclusion Homocysteine
promotes gluconeogenesis to enhance glucose output and contribute to the occurrence of insulin resistance.