No 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.

Background: Using untargeted metabolomics techniques, the goal of the study is to differentially screen serum and feces metabolite profiles of spontaneously diabetic and healthy cynomolgus monkeys, to explore potential serum and fecal biomarkers and analyze affected metabolic pathways.Methods: We adopted the diagnostic criteria for T2DM recommended by ADA for humans: FSG ≥7.0 mmol/L (126 mg/dl) and HbA1c ≥ 6.5%. The serum and feces samples from three diagnosed spontaneously T2DM cynomolgus monkeys and 11 agematched healthy controls were enrolled in the study. We employed LC-MS/MS-based untargeted metabolomic methods to reveal the differential metabolite profiles of serum and feces samples between the two groups and to analyze the affected metabolic pathways in MetaboAnalyst 5.0 based on KEGG library.Results: Six and 44 differential metabolites were identified in serum and feces samples, respectively, and the corresponding affected commonly metabolic pathways involved several metabolic ways, such as arginine biosynthesis, pantothenate and CoA biosynthesis, alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine biosynthesis, and histidine metabolism. Conclusion:The differential potential serum and feces biomarkers obtained from the LC-MS/MS based untargeted metabolomic may help to explain the potential pathophysiological mechanisms of T2DM and offer pivotal information for the early diagnosis and treatment of DM.

No abstract

Background: There has been no report on convergent local abnormalities of multiple functional brain imaging modalities including β-amyloid (Aβ) deposition, glucose metabolism, and resting-state functional magnetic resonance imaging (RS-fMRI) activities for participants with subjective cognitive decline (SCD). Methods: Fifty participants with SCD and 15 normal controls (NC) were scanned with both [18F]-florbetapir positron emission tomography (PET) and [18F]-fluorodeoxyglucose PET, each PET sacn accompanied with simultaneous RS-fMRI. Voxel-wise metrics were analyzed, including Aβ deposition, glucose metabolism, and three local metrics for RS-fMRI, i.e., amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC). Results: The SCD group showed increased Aβ deposition and increased glucose metabolism (P < 0.05, corrected), as well as decreased ALFF, ReHo, and DC (P < 0.05, uncorrected) in the same area of the left dorsal precuneus (dPCu). The dPCu showed negative resting state functional connectivity (RSFC) with the default mode network (DMN). Regarding global Aβ deposition positivity, the Aβ deposition in the dPCu showed a gradient change, i.e., SCD+ > SCD- > NC-. Further, both SCD+ and SCD- showed increased glucose metabolism and decreased RS-fMRI metrics in the dPCu. Conclusions: The convergent abnormal activities in the dPCu of SCD indicate that the dPCu is an early vulnerable region. The anti-RSFC of the dPCu with DMN supports that the earliest symptoms might be more related to other cognitive functions (e.g., unfocused attention) than episodic memory. (Funded by the National Key Research and Development Program of China and others; ClinicalTrials.gov number, NCT03370744.)