Niu Liqiong, Chen Qu, Hua Canfeng, Geng Yali, Cai Liuping, Tao Shiyu, Ni Yingdong, Zhao Ruqian
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, 210095 People's Republic of China.
J Anim Sci Biotechnol. 2018 Mar 16;9:26. doi: 10.1186/s40104-018-0242-4. eCollection 2018.
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.
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 ( < 0.05). Additionally, the content of hepatic glycogen was also markedly increased in Dex-treated goats ( < 0.01), while the content of glycogen in dorsal longissimus was unchanged by Dex ( > 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 (), sodium-glucose transporter 1 () and sodium-potassium ATPase () in the small intestine were generally increased by Dex, and mRNA expression was significantly up-regulated ( < 0.05). In liver, the expression of genes involved in gluconeogenesis including glucose-6-phosphatase catalytic subunit (), cytosolic form of phosphoenolpyruvate carboxykinase () and pyruvate carboxylase (), 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 mRNA expression of genes associated with gluconeogenesis and the insulin signaling pathway were generally up-regulated by Dex, but the mRNA expression of two markers of muscle atrophy, namely F-box protein 32 () and muscle RING-finger protein 1 (), was not altered by Dex.
Taken together, these results indicate that chronic administration of a low dosage of Dex induces hyperglycemia mainly through gluconeogenesis activation in the goat liver.
地塞米松（Dex）是一种合成糖皮质激素，作为抗炎和免疫抑制剂，是全球动物和人类中最常用的药物之一。糖皮质激素（GC）对血糖水平和其他代谢状况有深远影响。然而，长期使用地塞米松对反刍动物葡萄糖代谢的影响仍不清楚。
将10只山羊随机分为两组：对照组山羊注射生理盐水，地塞米松处理组山羊每天肌肉注射0.2mg/kg地塞米松，持续21天。结果显示，给予地塞米松后血浆葡萄糖和胰岛素浓度显著升高（P<0.05）。此外，地塞米松处理组山羊肝糖原含量也显著增加（P<0.01），而背最长肌糖原含量未因地塞米松而改变（P>0.05）。通过实时PCR检测小肠、骨骼肌和肝脏中参与血糖调节的几个关键基因的表达。地塞米松通常会增加小肠中葡萄糖转运蛋白2（GLUT2）、钠-葡萄糖转运蛋白1（SGLT1）和钠-钾ATP酶（Na+-K+-ATPase）的表达，且SGLT1 mRNA表达显著上调（P<0.05）。在肝脏中，参与糖异生的基因，包括葡萄糖-6-磷酸酶催化亚基（G6PC）、胞质型磷酸烯醇式丙酮酸羧激酶（PCK1）和丙酮酸羧化酶（PC）的表达，被地塞米松显著下调。然而，地塞米松使PCK1和PCK2的蛋白表达水平显著增加，提示存在转录后调控。在背最长肌中，与糖异生和胰岛素信号通路相关的基因的mRNA表达通常被地塞米松上调，但肌肉萎缩的两个标志物，即F-box蛋白32（FBXO32）和肌肉环指蛋白1（MuRF1）的mRNA表达未因地塞米松而改变。
综上所述，这些结果表明，慢性给予低剂量地塞米松主要通过激活山羊肝脏中的糖异生诱导高血糖。
