Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Demiroglu Bilim University, Istanbul, Turkey.
Department of Medical Biology, Faculty of Cerrahpasa Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.
J Biochem Mol Toxicol. 2019 Oct;33(10):e22388. doi: 10.1002/jbt.22388. Epub 2019 Aug 30.
The aim of the study is to clarify the effect of ghrelin treatment on the messenger RNA (mRNA) expression of the cannabinoid receptor 1 (Cnr1/CB1) and glucagon-like peptide 1 receptor (Glp1r/GLP-1R) as well as microRNAs (miR)-122 and miR-33a in the liver of rats with type 2 diabetes mellitus (T2DM). Adult Sprague-Dawley rats were divided into three groups: control (n = 7), T2DM (n = 7), and treatment (n = 7). Control animals received tap water. T2DM was induced by feeding 10% fructose in drinking water for 2 weeks followed by a single injection of streptozotocin (40 mg/kg, intraperitoneally [IP]). In the treatment group, diabetic rats were injected ghrelin (25 μg/kg, IP) for 14 days. Serum lipid profiles were evaluated, and mRNA expression levels of Cnr1 and Glp1r in the liver were detected using quantitative real-time polymerase chain reaction (RT-qPCR). In addition, miR-122 and miR-33a levels were measured using RT-qPCR. Serum triglycerides, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol significantly increased in the T2DM group compared with control rats but ghrelin treatment showed no effect on serum lipid levels. The mRNA expression levels of Cnr1 and Glp1r decreased in the T2DM group compared with the control group. These reductions were significantly increased in the T2DM group treated with ghrelin. Furthermore, the increase in miR-33a expression level was reduced in the treatment group compared to rats with T2DM. Our findings suggested that ghrelin treatment may alter the mRNA expression levels of CB1 and GLP-1R in the liver of rats with T2DM. The mRNA levels of Cnr1 and Glp1r may inversely correlate with the expression level of miR-33a but not miR-122.
本研究旨在阐明胃饥饿素治疗对 2 型糖尿病（T2DM）大鼠肝脏中大麻素受体 1（Cnr1/CB1）和胰高血糖素样肽 1 受体（Glp1r/GLP-1R）的信使 RNA（mRNA）表达以及 microRNA（miR）-122 和 miR-33a 的影响。成年 Sprague-Dawley 大鼠分为三组：对照组（n=7）、T2DM 组（n=7）和治疗组（n=7）。对照组动物饮用自来水。T2DM 通过在饮用水中添加 10%果糖 2 周，然后腹腔内（IP）注射链脲佐菌素（40mg/kg）诱导。在治疗组，糖尿病大鼠连续 14 天 IP 注射胃饥饿素（25μg/kg）。评估血清脂质谱，采用实时定量聚合酶链反应（RT-qPCR）检测肝脏中 Cnr1 和 Glp1r 的 mRNA 表达水平。此外，采用 RT-qPCR 测量 miR-122 和 miR-33a 的水平。与对照组大鼠相比，T2DM 组的血清甘油三酯、低密度脂蛋白胆固醇和极低密度脂蛋白胆固醇水平显著升高，但胃饥饿素治疗对血清脂质水平没有影响。与对照组相比，T2DM 组 Cnr1 和 Glp1r 的 mRNA 表达水平降低。用胃饥饿素治疗后，T2DM 组的这些降低明显增加。此外，与 T2DM 大鼠相比，治疗组 miR-33a 表达水平的增加减少。我们的研究结果表明，胃饥饿素治疗可能改变 T2DM 大鼠肝脏中 CB1 和 GLP-1R 的 mRNA 表达水平。Cnr1 和 Glp1r 的 mRNA 水平可能与 miR-33a 的表达水平呈负相关，但与 miR-122 无关。
