GC/TOFMS analysis of metabolites in serum and urine reveals metabolic perturbation of TCA cycle in db/db mice involved in diabetic nephropathy

摘要

In addition to microalbuminuria, the range of renal injury biomarkers has been expanded to a set of urine proteins, cytokines, and genes. Several potential biomarkers, such as serum p2-microG, high sensitivity C-reaction protein (hsCRP), cystatin C (Cys C), hyaluronic acid (HA), laminin (LN), and tissue inhibitor of metalloproteinases 1 (TIMP-1), have been suggested as additional indicators of DN (20), but no further clinical application of them has yet been reported. In contrast, based on novel genomic studies, several gene candidates, including NEGR1, IRS2, RIPK2, and SHPK, have been recognized as involved in kidney damage, suggesting that they encode common underlying factors that predispose individuals to kidney disease through functional and structural changes in the renal glomerulus and tubules (31). In recent years, genetic studies using different animal models have shown that DN-associated genetic loci are often the genes that also underlie insulin resistance, obesity, hyperlipidemia, and cardiovascular diseases (11, 22), suggesting that the metabolic disorders involved in DM alter gene expression and predispose patients to renal complications. However, no specific gene has been associated with a large proportion of patients with DN. The lack of consistency and any link between these various genes have led to a failure to identify a genetic biomarker (5).