Background: Dexamethasone(Dex), a synthetic glucocorticoid, is among the most commonly used drugs worldwide in animals and humans as an anti-inflammatory and immunosuppressive agent. GC has profound effects on plasma ...Background: Dexamethasone(Dex), a synthetic glucocorticoid, is among the most commonly used drugs worldwide in animals and humans as an anti-inflammatory and immunosuppressive agent. GC has profound effects on plasma glucose level and other metabolic conditions. However, the effect of prolonged use of Dex on glucose metabolism in ruminants is still unclear.Results: Ten goats were randomly assigned to two groups: the control goats were injected with saline, and the Dex-treated goats were intramuscularly injected daily for 21 d with 0.2 mg/kg Dex. The results showed that plasma glucose and insulin concentrations were significantly increased after Dex administration(P < 0.05). Additionally, the content of hepatic glycogen was also markedly increased in Dex-treated goats(P < 0.01), while the content of glycogen in dorsal longissimus was unchanged by Dex(P > 0.05). The expression of several key genes, involved in blood glucose regulation, was detected by real-time PCR in the small intestine, skeletal muscle and liver. The expression of glucose transporter type 2(GLUT2), sodium-glucose transporter 1(SGLT1) and sodium-potassium ATPase(Na-K/ATPase) in the small intestine were generally increased by Dex, and GLUT2 m RNA expression was significantly up-regulated(P < 0.05). In liver, the expression of genes involved in gluconeogenesis including glucose-6-phosphatase catalytic subunit(G6 PC), cytosolic form of phosphoenolpyruvate carboxykinase(PCK1) and pyruvate carboxylase(PC), were significantly down-regulated by Dex. However, the protein expression levels of PCK1 & PCK2 were significantly increased by Dex, suggesting a post-transcriptional regulation. In dorsal longissimus, the m RNA expression of genes associated with gluconeogenesis and the insulin signaling pathway were generally upregulated by Dex, but the m RNA expression of two markers of muscle atrophy, namely F-box protein 32(FBXO32/Atrogin1) and muscle RING-finger protein 1(Mu RF1), was not altered by Dex.Conclusions: Taken together, these results indicate that chronic administration of a low dosage of Dex induces hyperglycemia mainly through gluconeogenesis activation in the goat liver.展开更多
基金supported by the National Nature Science Foundation of China(project no.31572433)the Program for New Century Excellent Talents in University(NCET-13-0862)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Background: Dexamethasone(Dex), a synthetic glucocorticoid, is among the most commonly used drugs worldwide in animals and humans as an anti-inflammatory and immunosuppressive agent. GC has profound effects on plasma glucose level and other metabolic conditions. However, the effect of prolonged use of Dex on glucose metabolism in ruminants is still unclear.Results: Ten goats were randomly assigned to two groups: the control goats were injected with saline, and the Dex-treated goats were intramuscularly injected daily for 21 d with 0.2 mg/kg Dex. The results showed that plasma glucose and insulin concentrations were significantly increased after Dex administration(P < 0.05). Additionally, the content of hepatic glycogen was also markedly increased in Dex-treated goats(P < 0.01), while the content of glycogen in dorsal longissimus was unchanged by Dex(P > 0.05). The expression of several key genes, involved in blood glucose regulation, was detected by real-time PCR in the small intestine, skeletal muscle and liver. The expression of glucose transporter type 2(GLUT2), sodium-glucose transporter 1(SGLT1) and sodium-potassium ATPase(Na-K/ATPase) in the small intestine were generally increased by Dex, and GLUT2 m RNA expression was significantly up-regulated(P < 0.05). In liver, the expression of genes involved in gluconeogenesis including glucose-6-phosphatase catalytic subunit(G6 PC), cytosolic form of phosphoenolpyruvate carboxykinase(PCK1) and pyruvate carboxylase(PC), were significantly down-regulated by Dex. However, the protein expression levels of PCK1 & PCK2 were significantly increased by Dex, suggesting a post-transcriptional regulation. In dorsal longissimus, the m RNA expression of genes associated with gluconeogenesis and the insulin signaling pathway were generally upregulated by Dex, but the m RNA expression of two markers of muscle atrophy, namely F-box protein 32(FBXO32/Atrogin1) and muscle RING-finger protein 1(Mu RF1), was not altered by Dex.Conclusions: Taken together, these results indicate that chronic administration of a low dosage of Dex induces hyperglycemia mainly through gluconeogenesis activation in the goat liver.
