Comparative analysis of the transcriptome of T2DM Bama mini-pigs with T2DM patients

Objective To compare the transcriptional differences between the T2DM-susceptible and T2DM-tolerant Bama mini-pigs and to determine the utility of Bama mini-pigs as an animal model for T2DM by comparing the transcriptomes of the animals with T2DM patients. Methods The skeletal muscle transcriptomes of healthy Guangxi Bama mini-pigs (CON), T2DM pigs (T2D), and non-T2DM pigs (NT2D) were determined by RNA sequencing. Results A total of 290 differentially expressed genes (DEGs) were detected in NT2D relative to the CON groups, 572 DEGs in T2D compared to CON, and 300 DEGs in T2D compared to NT2D. The RNA-seq data was verified by qPCR analysis of PGC1 alpha, NR4A3, CSRP3, MYH7, MYH2, MYH1, GLUT4, PPAR gamma, LEP, ATP5H, UCP2, and MTOR transcripts. The DEGs in T2D Bama mini-pigs were mainly involved in signaling pathways associated with metabolism, cardiovascular diseases, infectious disease, cancer, inflammation and immune responses, cytoskeleton, and signal transduction. Comparative analysis of the transcriptomes of T2DM Bama mini-pigs and T2DM patients (GSE29221 dataset) revealed 17 differentially co-expressed genes that were assigned to 11 GO terms and 6 annotated pathways, including hypertrophic cardiomyopathy, dilated cardiomyopathy, thyroid cancer, cardiac muscle contraction, tight junction, and calcium signaling pathway, suggesting that the T2D Bama mini-pigs could be used on T2DM research in those pathways. Conclusion This study represents the first RNAseq transcriptome analysis in T2D Bama mini-pigs and provided a new perspective for the study on the human T2DM pathogenesis by using the T2DM model of Bama mini-pigs.