Proteomic Analysis of Serum Biomarkers for Pre‐Diabetes Using the LEA Rat, a Spontaneous Animal Model of Type 2 Diabetes Mellitus

Aim To identify candidate serum molecules associated with the progression of type 2 diabetes mellitus (T2DM), differential serum proteomic analysis was performed on a spontaneous animal model of T2DM without obesity, the Long-Evans Agouti (LEA) rat. Materials and methods We performed quantitative proteomic analysis using serum samples from 8- and 16-week-old LEA and control Brown Norway (BN) rats (n=4/group). Differentially expressed proteins were validated by multiple reaction monitoring (MRM) analysis using the sera collected from 8-, 16- and 24-week-old LEA (n = 4/each group) and BN rats [n = 5/each group]. Among the validated proteins, we also examined the possible relevance of the human homologs of SERPINA3 to T2DM. Results 2D-DIGE analysis and the following LC-MRM analysis revealed that the serum levels of 5 proteins were differentially changed between LEA rat and BN rat at all three time points examined. Among the 5 proteins, SERPINA3N were increased significantly in the sera of LEA rats compared with age-matched BN rats. The serum level of SERPINA3 was also found to be significantly higher in T2DM patients than in healthy control subjects. Moreover, HbA1c, fasting insulin, and eGFR were independently associated with the SERPINA3 levels. Conclusions These findings suggest a possible role for SERPINA3 in the development of the early stages of T2DM although further replication studies and functional investigations regarding their role are needed. This article is protected by copyright. All rights reserved.