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Differential proteome analysis of serum proteins associated with the development of type 2 diabetes mellitus in the KK-Ay mouse model using the iTRAQ technique

Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.
Journal of proteomics (Impact Factor: 3.93). 03/2013; DOI: 10.1016/j.jprot.2013.03.014
Source: PubMed

ABSTRACT To identify candidate serum molecules associated with the progression of type 2 diabetes mellitus (T2DM), we carried out differential proteomic analysis using the KK-Ay mouse, an animal model of T2DM with obesity. We employed an iTRAQ-based quantitative proteomic approach to analyze the proteomic changes in the sera collected from a pair of 4-week-old KK-Ay versus C57BL/6 mice. Among the 227 proteins identified, a total of 45 proteins were differentially expressed in KK-Ay versus C57BL/6 mice. We comparatively analyzed a series of the sera collected at 4 and 12 weeks of age from KK-Ay and C57BL/6 mice for the target protein using multiple reaction monitoring analysis, and identified 8 differentially expressed proteins between the sera of these mice at both time points. Among them, serine (or cysteine) peptidase inhibitor, clade A, member 3K (SERPINA3K) levels were elevated significantly in the sera of KK-Ay mice compared to C57BL/6 mice. An in vitro assay revealed that the human homologue SERPINA3 increased the transendothelial permeability of retinal microvascular endothelial cells, which may be involved in the pathogenesis of diabetes and/or diabetic retinopathy. With the identified proteins, our proteomics study could provide valuable clues for a better understanding of the underlying mechanisms associated with T2DM.

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