Changes in the expression levels of CB1 and GLP-1R mRNAs and microRNAs 33a and 122 in the liver of type 2 diabetic rats treated with ghrelin.

Abstract

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.