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.