Omics reveal the difference between PTDM and T2D among the liver, pancreas and adipose tissue

Abstract

Backgroud: This research delved into the underlying mechanisms responsible for post-transplant diabetes mellitus (PTDM) and comparisons with type 2 diabetes (T2D). Methods: Comprehensive analyses, encompassing both transcriptomics and metabolomics, were conducted on liver and pancreatic tissues from the PTDM and T2D groups. Furthermore, distinctions in competing endogenous RNA (ceRNA) networks were explored. Weighted gene co-expression network analysis (WGCNA)was implemented to identify clusters of genes exhibiting strong correlations among the liver, pancreas, and adipose tissue. Results: Compared to their T2D counterparts, PTDM mice exhibited notable differences in higher body weight (P <0.05), lower blood glucose levels (P <0.05), and enhanced insulin tolerance (P <0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated significant alterations in the MAPK pathway and leukocyte migration within the liver, as well as variations in the differentiation of Th17, Th1, and Th2 cells, along with T cell activation, within the pancreas. In addition, the MAPK signaling pathway and leukocyte migration pathways were significantly modified in adipose tissue. The ceRNA network analysis highlighted substantial changes, revealing 164 long intergenic non-coding RNA (lincRNA) and 154 circular RNA (circRNA) networks significantly changed in the liver, and 445 lincRNA and 135 circRNA networks in the pancreas that were significantly altered in the PTDM group compared to T2D group. Notably, the metabolites Resveratrol, Aldehydo-D-xylose, 3-Hydroxybutyric acid, 5-Aminoimidazole-4-carboxamide, Leucinic acid and (R)-lipoic acid displayed significant changes in the liver in PTDM mice, with their regulation attributed to 2510002D24RIK. Conclusion:In summary, PTDM mice exhibited distinctive multi-omics and pathological characteristics compared to their T2D counterparts.