Metalloproteins and apolipoprotein C: candidate plasma biomarkers of T2DM screened by comparative proteomics and lipidomics in ZDF rats

Abstract

Background: Early diagnosis of type 2 diabetes mellitus (T2DM) is still difficult. Screening of plasma biomarkers has great significance of optimizing diagnosis and predicting the complications of T2DM. Methods: We used a special diet, Purina #5008, to induce diabetes in Zucker leptin receptor gene-deficient rats (fa/ fa) to establish Zucker diabetic fatty (ZDF) rats, simulating the early stage of T2DM. The differentially expressed proteins (DEP) and lipids (DEL), as potential biomarkers, were screened to compare the plasma expression levels in ZDF rats and their basic diet-fed wild-type controls (fa/+) by Tandem Mass Tags (TMT) and liquid chromatographytandem mass spectrometry. Results: These two groups had different plasma proteins and lipids profiles consisting of 84 DEPs and, 179 DELs identified in the positive ion mode and 178 DELs in the negative ion mode, respectively. Enrichment analysis of these different indicators showed that oxidative stress, insulin resistance and metabolic disorders of glycan and lipid played an important role in generating the difference. Some markers can be used as candidate biomarkers in prediction and treatments of T2DM, such as ceruloplasmin, apolipoprotein C-I, apolipoprotein C-II and apolipoprotein C-IV. Conclusion: These plasma differences help to optimize the diagnosis and predict the complications of T2DM, although this remains to be verified in the crowd. Trace elements related-metalloproteins, such as ceruloplasmin, and lipid metabolism and transport-related apolipoprotein C are expected to be candidate biomarkers of T2DM and should be given more attention.

Reduced SV2A and GABAAreceptor levels in the brains of type 2 diabetic rats revealed by [18F]SDM-8 and [18F]flumazenil PET

“…Our finding of reduced cortical levels of SV2A measured by [ 18 F]SDM-8 in the brains of aged ZDF rats compared to SD rats corroborated our findings of downregulation of the synaptic-related proteins Dbnl, Syn1, Syn2, and Map2 and synaptic-related pathways in hippocampal tissues from 12-monthold ZDF rats compared to SD rats. This is in line with earlier biochemical studies [5][6][7], and proteomic studies in the hippocampus of ZDF rats identified reductions in the levels of the metalloproteins apolipoprotein C, myelin binding protein and apolipoprotein A-I as well as the synaptic proteins Mapk1, OMG, Gng12, Dbnl, sv2a, and Stx12 [41][42][43].…”

“…In addition, a comprehensive bioinformatics analysis was used to investigate the differentially expressed proteins and enriched signaling pathways as described earlier [41][42][43]. We analysed the differentially expressed genes (DEPs) by using principal component analysis (PCA), volcano plot analysis, subcellular localization analysis, Cluster of Orthologous Groups of proteins (COG) analysis, kinase analysis, proteomic and peptide assays, (Kyoto Encyclopedia of Genes and Genomes, KEGG) signaling pathways, modification site assay, differential gene expression analysis, and gene ontology (GO) analysis.…”

Identifying potential therapeutic targets of mulberry leaf extract for the treatment of type 2 diabetes: a TMT-based quantitative proteomic analysis

“…Cp is a ferroxidase that plays a crucial role in the oxidation of Fe 2+ to Fe 3+ , thereby binding iron to transferrin and promoting iron mobilization in the body [ 55 ]. Cp synthesis and/or secretion can be altered by inflammation and insulin, and Cp levels are positively associated with hyperglycemia and IR [ 56 , 57 ]. Fth is an important iron storage protein in the body [ 58 ].…”

Multi-omics: Opportunities for research on mechanism of type 2 diabetes mellitus

“…Using multi-omics, our previous research[ 5 , 6 ] described the intestinal flora alterations and the plasma protein metabolic profile perturbations in the Zucker diabetic fatty rat, which is a spontaneous T2DM animal model commonly used to develop drugs for treating diabetes[ 7 - 10 ]. The altered intestinal microbiota and differentially expressed proteins and metabolites clearly distinguished the treatment group [T: Zucker leptin receptor gene-deficient rats (fa/fa) treated by Purina #5008] from the control group [C: basic diet-fed litter mate wild-type controls (fa/+)].…”

“…Copyright ©The Author(s) 2020. Published by Springer Nature[ 6 ]. T: Zucker leptin receptor gene-deficient rats (fa/fa) treated by Purina #5008 for 3 wk; C: Basic diet-fed litter mate wild-type controls (fa/+); DEPs: Differentially expressed proteins; T2DM: Type 2 diabetes mellitus.…”