AbstractBackgroundInsulin‐like factor 3 (INSL3) was stated to be an essential regulator in many diseases. This present study aimed to explore the underlying mechanisms of INSL3 in diabetic nephropathy (DN).MethodsThe serum samples were obtained from 121 DN patients, 67 T2DM patients, and 44 healthy controls. Twenty SD rats were used to establish the DN model in vivo. Quantitative PCR (qPCR) and Western blot were completed to analyze the INSL3 expression in cells, serum samples, and kidney of the rats. The structure of kidney was analyzed by HE staining. The diagnostic values of INSL3 in DN were determined by receiver operating characteristic (ROC) assay. Then, Spearman's correlation analysis was executed to verify the association between INSL3 and glomerular filtration rate (eGFR). Finally, the proliferation and apoptosis status of transfected cells were analyzed by MTT, flow cytometry, and Hoechst33258 staining assay.ResultsWe found that INSL3 expression was up‐regulated in DN patients and SV40‐MES‐13 cells. Furthermore, the correlation analysis elucidated that INSL3 expression was negatively correlated with DN diagnosis golden criterion eGFR. INSL3 knockdown promoted the proliferation rate and inhibited the apoptosis rate of SV40‐MES‐13 cells after high‐glucose treatment. Finally, the INSL3 expression and fast blood glucose were up‐regulated in DN rats.ConclusionsCollectively, this study demonstrated the clinical significance of INSL3 in diagnosing and developing DN.