Quantitative Proteomic Analysis of Serum Reveals MST1 as a Potential Candidate Biomarker in Spontaneously Diabetic Cynomolgus Monkeys

Abstract

The prevalence of type 2 diabetes (T2DM) is increasing globally, creating essential demands for T2DM animal models for the study of disease pathogenesis, prevention, and therapy. A non-human primate model such as cynomolgus monkeys can develop T2DM spontaneously in an age-dependent way similar to humans. In this study, a data-independent acquisition-based quantitative proteomics strategy was employed to investigate the serum proteomic profiles of spontaneously diabetic cynomolgus monkeys compared with healthy controls. The results revealed significant differences in protein abundances. A total of 95 differentially expressed proteins (DEPs) were quantitatively identified in the current study, among which 31 and 64 proteins were significantly upregulated and downregulated, respectively. Bioinformatic analysis revealed that carbohydrate digestion and absorption was the top enriched pathway by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Protein− protein interaction network analysis demonstrated that MST1 was identified as the most connected protein in the network and could be considered as the hub protein. MST1 was significantly and inversely associated with FSG and HbA1c. Furthermore, recent lines of evidence also indicate that MST1 acts as a crucial regulator in regulating hepatic gluconeogenesis to maintain metabolic homeostasis while simultaneously suppressing the inflammatory processes. In conclusion, our study provides novel insights into serum proteome changes in spontaneously diabetic cynomolgus monkeys and points out that the dysregulation of several DEPs may play an important role in the pathogenesis of T2DM.

Association of MST1 in the First Trimester of Pregnancy with Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes

“…24 In a retrospective cohort study involved 160 patients with acute type A aortic dissection (ATAAD), the greater circulating MST1 detected using ELISA was correlated with the 30-day mortality in these patients who underwent emergency surgery. 25 …”

Combined untargeted and targeted lipidomics approaches reveal potential biomarkers in type 2 diabetes mellitus cynomolgus monkeys

“…A total of 15 male cynomolgus monkeys including seven naturally occurring T2DM cynomolgus monkeys (referred as disease group), combined with eight healthy cynomolgus monkeys matched with similar age (referred as healthy group), were included in the study. The diagnostic criteria for identifying T2DM cynomolgus monkeys and healthy cynomolgus monkeys have been described in our previous publication 20 . The cynomolgus monkeys used in this study were provided by Hainan Jingang Biotech Co. Ltd. (Hainan, China), which is a fully accredited facility by AAALAC International.…”

“…The diagnostic criteria for identifying T2DM cynomolgus monkeys and healthy cynomolgus monkeys have been described in our previous publication. 20 The cynomolgus monkeys used in this study were provided by Hainan Jingang Biotech Co. Ltd. After an overnight fast, the whole-blood samples were collected in the serum separation tubes. After coagulation of blood for 1 h, the tubes were centrifuged at 1500×g for 10 min at 4°C, the serum was separated, the supernatants were then re-collected and placed into freehold tubes, immediately cooled in liquid nitrogen and stored at −80°C until further processing.…”

“…NHPs play a crucial role as a translational bridge, linking fundamental studies conducted in rodent models to clinical investigations in humans because of their anatomical, physiological, and genetic similarities to humans 19 . Cynomolgus monkeys ( Macaca fascicularis ), as a most commonly used NHP species, can naturally occurring T2DM in an age‐dependent manner like humans, and the demand for utilizing cynomolgus monkeys as models in T2DM research is steadily increasing 20 . To date, there have been limited studies on the serum lipidome of T2DM cynomolgus monkeys.…”

“…19 Cynomolgus monkeys (Macaca fascicularis), as a most commonly used NHP species, can naturally occurring T2DM in an age-dependent manner like humans, and the demand for utilizing cynomolgus monkeys as models in T2DM research is steadily increasing. 20 To date, there have been limited studies on the serum lipidome of T2DM cynomolgus monkeys.…”