The application of post-translational modification oriented serum proteomics to assess experimental diabetes with complications

Abstract

Proteome analysis of serum from type 2 diabetics with complications may lead to the discovery of diagnostic or prognostic biomarkers. To circumvent the principal barrier of serum proteomics, our investigation aimed to evaluate whether a study of post-translational modification enriched serum proteins could be valuable for the discovery of biomarkers or metabolic pathways related to type 2 diabetes pathogenesis. Type 2 diabetes was induced from high-fat diet fed Sprague Dawley rats with streptozotocin injection. Once diabetic status was confirmed, serum samples from either fasted healthy or diabetic rats were pooled and profiled by two-dimensional difference gel electrophoresis or comparative 2D electrophoresis after protein enrichments using immobilized metal ion, concanavalin A, and lentil affinity chromatography, respectively. Differential expressed proteins were identified and the associated networks were established by an Ingenuity Pathway Analysis. As a result, induced rats became severe diabetic and accompanied by hyperlipidemia, fatty liver, and glomerular hypertrophy. There were 3 total, 14 phosphorylated and 23 glycosylated protein targets differentially expressed. Proteins could be linked to HNF4A, HNF1A, and NFκB transcriptional factors and antigen presentation, humoral immune response, and inflammatory response pathways. Predicted organ toxicity in kidney, heart, and liver matched with our histopathological results. In conclusion, post-translational modification based serum protein enrichment could be a valuable approach to enhance the resolution of serum proteomics without depleting potentially valuable abundant proteins. Our results also indicated the potential association of the hepatic secretome and hepatocyte nuclear factors in the pathogenesis of type 2 diabetes and its complications.

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

“…So far, very limited studies have been performed with regard to detection of plasma proteins and lipids profiles in ZDF rats. Therefore, this study may provide a novel strategy to characterize the molecular mechanism of T2DM and search for potential biomarkers [54,59,60], despite the fact that this is only at the animal level. It is notable that the samples number is small, although this is sufficient for LC-MS/MS analysis.…”

Polyphenol-Rich Leaf of Annona squamosa Stimulates Insulin Release from BRIN-BD11 Cells and Isolated Mouse Islets, Reduces (CH2O)n Digestion and Absorption, and Improves Glucose Tolerance and GLP-1 (7-36) Levels in High-Fat-Fed Rats

“…Insulin glycation is a key post-translational alteration in the pathogenesis of diabetes that can lead to long-term problems [ 47 ]. The glycation of proteins with short half-lives, such as insulin, can lead to the formation of advanced glycation end products (AGEs), resulting in insulin resistance [ 48 , 49 , 50 ].…”

Evaluation of the Antidiabetic and Insulin Releasing Effects of A. squamosa, Including Isolation and Characterization of Active Phytochemicals

“…Glycation is a common post translational modification of proteins in diabetes and is strongly implicated in the genesis of long-term complications [ 42 ]. Insulin glycation is an example of glycation of short-lived protein that can lead to insulin resistance because of its reduced biological activity [ 43 ].…”