Proteomic Study on the New Potential Mechanism and Biomarkers of Diabetes.

PURPOSE: Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia. So far, the pathogenesis of diabetes has not been fully elucidated. Identifying new potential molecule mechanisms and biomarkers in this process could contribute to the understanding of pathophysiology.

EXPERIMENTAL DESIGN: Proteomic changes in the liver of type 2 diabetic mice (n = 6) and normal mice (n = 6) are studied. Triplicate experiments are carried out for each sample.

RESULTS: A total of 15 differentially expressed proteins (DEPS ) are identified and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicates that DEPS mainly involved two inflammatory pathways: glutathione metabolic pathway and the arachidonic acid metabolic pathway. The core of protein-protein interaction is the tumor necrosis factor inflammatory pathway, indicating the connection between inflammation and diabetes. Ten out of fifteen gene transcript levels are consistent with proteomics by quantitative RT-PCR validation. The transcriptional levels of OAT (ornithine aminotransferase) and fructose-1,6-bisphosphatase1 (FBP1) were significantly increased, whereas fatty acid binding protein 5 (FABP5) and ef-2 transcription levels decreased significantly. In addition, western blotting results showed that the expression of OAT and FBP protein increased significantly in the diabetes group, while elongation factor 2 decreased significantly and FABP do not have significant difference in the diabetes group.

CONCLUSIONS AND CLINICAL RELEVANCE: Taken together, the present exploratory liver proteomic analysis might be seen as an important starting point for studies targeting specific liver proteins aimed at the implementation of new biomarkers for the early detection of type 2 diabetes mellitus-related potential mechanisms, hoping to provide biomarkers and clinical therapeutic targets of type 2 diabetes mellitus.