【Animal modeling】-The effect of liraglutide on the expression and mechanism of key enzymes PEPCK and G6pase in hepatic gluconeogenesis in diabetic mice

  Objective To observe the effect and mechanism of liraglutide on the expression of key enzymes glucose-6-phosphate (G-6-Pase) and phosphoenolpyruvate carboxylase (PEPCK) in hepatic gluconeogenesis in diabetic mice.

  Methods Animal experiment design was divided into 3 groups: normal control group (male C57 mice, n=5), intraperitoneal injection of normal saline; model control group (male KK-Ay diabetic mice, n=5), intraperitoneal injection of normal saline; In the laglutide intervention group (male KK-Ay diabetic mice + drug intervention, n=5), liraglutide was injected intraperitoneally. All three groups of mice were reared in the same rearing environment. After 8 weeks of intervention, the blood sugar of the mice was detected, and Western blot was used to detect FOXO1, cryptochrome 1 (CRY1), E3 ubiquitin protease DDB1, and the key gluconeogenesis enzyme glucose-6-phosphatase (G-6- Pase) and phosphoenolpyruvate carboxylase (PEPCK).

  Results Compared with the model control group, blood glucose in the liraglutide intervention group was significantly decreased; after liraglutide intervention, the expressions of DDB1, FOXO1, G6Pase and PEPCK in the liver of diabetic mice decreased, while the expressions of cryptochrome 1 (CRY1) expression increased.

  Conclusion Liraglutide can down-regulate the expression of key hepatic gluconeogenesis enzymes G6Pase and PEPCK in diabetic mice, and its effect may be related to the down-regulation of E3 ubiquitin protease DDB1.