Department of Biotechnology, St Joseph's College, Irinjalakuda 680 121, Thrissur District, Kerala, India.
Br J Nutr. 2012 Oct 28;108(8):1410-8. doi: 10.1017/S0007114511006830. Epub 2012 Jan 6.
Diabetes mellitus is a growing health problem worldwide and is associated with severe liver complications. The aim of the present study is to analyse the status of metabolic and free-radical-scavenging enzymes and second messengers in the liver of streptozotocin (STZ)-induced diabetic rats, and to determine the hepatoprotective role of vitamin D(3). All studies were performed using the liver of adult male Wistar rats. Gene expression studies were carried out using real-time PCR with specific probes. Second messenger levels were determined using (3)H-labelled Biotrak assay kits, and glucose uptake assay with D-[(14)C]glucose. The present results show that there was a decrease in hepatic glucose uptake, malate dehydrogenase activity, glycogen content, inositol triphosphate (IP(3)) and cyclic GMP levels, and superoxide dismutase, glutathione peroxidase, phospholipase C, cyclic AMP-responsive element-binding protein, vitamin D receptor (VDR) and insulin receptor (INSR) gene expression in the diabetic rats when compared with the controls (all P < 0·05), while cyclic AMP levels and GLUT2 expression were increased (P < 0·05). Treatment of the diabetic rats with vitamin D(3) and insulin reversed the altered parameters to near control values. In conclusion, the data suggest a novel role of vitamin D(3) in restoring impaired liver metabolism in STZ-induced diabetic rats by regulating glucose uptake, storage and metabolism. We demonstrated that the restoring effect of vitamin D(3) is mediated through VDR modulation, thereby improving signal transduction and controlling free radicals in the liver of diabetic rats. These data suggest a potential role for vitamin D(3) in the treatment of diabetes-associated hepatic complications.
糖尿病是全球范围内日益严重的健康问题，与严重的肝脏并发症有关。本研究旨在分析链脲佐菌素（STZ）诱导的糖尿病大鼠肝脏中代谢和自由基清除酶及第二信使的状态，并确定维生素 D（3）的肝保护作用。所有研究均使用成年雄性 Wistar 大鼠的肝脏进行。使用实时 PCR 结合特异性探针进行基因表达研究。使用（3）H 标记的 Biotrak 测定试剂盒和 D-[(14)C]葡萄糖摄取测定法测定第二信使水平。本研究结果表明，与对照组相比，糖尿病大鼠肝脏葡萄糖摄取、苹果酸脱氢酶活性、糖原含量、三磷酸肌醇（IP（3））和环鸟苷酸水平降低，超氧化物歧化酶、谷胱甘肽过氧化物酶、磷脂酶 C、环腺苷酸反应元件结合蛋白、维生素 D 受体（VDR）和胰岛素受体（INSR）基因表达降低（均 P < 0·05），而环腺苷酸水平和 GLUT2 表达增加（P < 0·05）。用维生素 D（3）和胰岛素治疗糖尿病大鼠可使改变的参数恢复到接近对照值。综上所述，数据表明维生素 D（3）通过调节葡萄糖摄取、储存和代谢，在恢复 STZ 诱导的糖尿病大鼠受损肝脏代谢方面具有新的作用。我们证明，维生素 D（3）的恢复作用是通过 VDR 调节介导的，从而改善了糖尿病大鼠肝脏中的信号转导和自由基控制。这些数据表明维生素 D（3）在治疗与糖尿病相关的肝脏并发症方面具有潜在作用。
