Analysis of the Relationship Between Serum Nesfatin-1 Concentration and Diabetic Nephropathy Disease Activity Factors

Background: Recently, NUCB2/Nesfatin-1 (NES-1) has been reported not only as a novel satiety factor but also for its multifaceted effects in regulating gastrointestinal function, glucose and lipid metabolism, and cardiovascular system. We have reported that serum NES-1 concentration in DKD (including diabetic nephropathy) is negatively correlated with tubular tissue damage and positively correlated with renal prognosis. In this study, we investigated the relationship between serum NES-1 concentration and diabetic nephropathy disease activity factors. Methods: We measured sNES-1 by ELISA in 63 patients diagnosed with DKD (including DM nephropathy) who underwent renal biopsy between January 2013 and December 2023 at our hospital, and randomly selected 6 patients each (3 males and 3 females) into 3 groups (high, normal and low levels), and analyzed their serum and urine by LC/MS (DDA and DIA methods) were analyzed and compared. Results: LC/MS analysis of serum showed that VAP1 (vascular cell adhesion protein 1) and Cadherin-5 were low in the group with low NES-1 levels. Urine LC/MS analysis showed low levels of ICOS Ligand (Inducible T-cell Co-Stimulator Ligand) and vasorin in the low NES-1 group. LASP1 (LIM and SH3 domain protein 1) and 28S ribosomal protein S12 were higher in the high NES-1 group than in the normal NES-1 group. Furthermore, there was no significant difference between male and female subjects. Conclusion: Low serum NES-1 levels in diabetic kidney disease may result in low levels of vasorin (urine), which protects the kidney from ischemia and reperfusion by regulating the HIF-1a/MAPK signaling pathway, leading to renal injury (especially in the renal tubules) and progressive anemia. Similarly, low serum NES-1 levels were associated with low levels of VAP-1 (serum), an adhesion molecule expressed on vascular endothelial cells, which may be involved in the progression of diabetes and the development of complications. These results suggest that serum NES-1 levels may be involved in the pathogenesis of diabetes-related kidney disease and may be a potential therapeutic target. Funding: NIDDK Support