Urinary insulin signaling pathway related proteins may serve as potential biomarkers for monitoring diabetes mellitus without hypertension and hyperlipidemia.

The insulin signaling pathway plays an important role in the development of diabetes mellitus. The expression of insulin signaling pathway related proteins in the urine of diabetic patients has not been reported. The aim of this study was to analyze and verify the expression of insulin signaling pathway related proteins in the urine of diabetic patients without hypertension and hyperlipidemia, and to explore their clinical application value. Based on data-independent acquisition proteomics technology and bioinformatics, the urinary protein expression profile of diabetic patients without hypertension and hyperlipidemia was established. Western blot and enzyme-linked immunoassay were performed to verify the expression of insulin signaling pathway related proteins in the urine of diabetic patients. Sixteen proteins related to the insulin signaling pathway were screened in urine, and 7 of them were differentially expressed in the urine of diabetic patients without hypertension and hyperlipidemia. Further quantitative analysis showed that the downregulation of protein kinase CAMP-dependent type II regulatory subunit α, growth factor receptor bound protein 2, and guanine nucleotide-binding protein G(s) in the urine of diabetic patients without hyperlipidemia and hypertension was consistent with the preliminary screening results. In this exploratory study, we detected the expression of insulin signaling pathway related proteins in the urine of diabetic patients without hypertension and hyperlipidemia. protein kinase CAMP-dependent type II regulatory subunit α, growth factor receptor bound protein 2, and guanine nucleotide-binding protein G(s) in the urine of diabetic patients were downregulated, which was associated with diabetes. They may be promising noninvasive biomarkers for monitoring diabetes.