BACKGROUND: The aim of this study was to explore the potential therapeutic targets and pathways of liraglutide against type 2 diabetes mellitus (T2DM) in streptozotocin-induced diabetic rats based on lncRNA sequencing.

MATERIAL AND METHODS: Male Wistar rats were randomly divided into 3 groups: the control group (n=10), the T2DM model group (high-sugar and high-fat diet, and streptozotocin-induced, n=11), and the liraglutide group (model plus liraglutide, n=10). After 8 weeks of drug treatment, lncRNA sequencing was used to identify the lncRNA therapeutic targets and their related protein-coding genes of liraglutide against T2DM, which were further studied by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to determine the major biological processes and pathways involved in the action of liraglutide treatment. Lastly, several lncRNA targets were randomly detected based on quantitative real-time polymerase chain reaction (QRT-PCR) to verify the accuracy of sequencing results.

RESULTS: A total of 104 lncRNA targets of liraglutide against T2DM were screened, with 27 upregulated and 77 downregulated, including NONRATT030354.2, MSTRG.1456.6, and NONRATT011758.2. The major biological processes involved were glucose and lipid metabolism and amino acid metabolism. Liraglutide had a therapeutic effect in T2DM, mainly through the Wnt, PPAR, amino acid metabolism signaling, mTOR, and lipid metabolism-related pathways.

CONCLUSIONS: In this study, we screened 104 lncRNA therapeutic targets and several signaling pathways (Wnt, PPAR, amino acid metabolism signaling pathway, mTOR, and lipid metabolism-related pathways) of liraglutide against T2DM based on lncRNA sequencing.

Keywords: Diabetes Mellitus, Type 2, Gene Targeting, Blood Glucose, Diabetes Mellitus, Experimental, Diet, High-Fat, Gene Expression Regulation, Hypoglycemic Agents, liraglutide