Multi-omics Profiling of Diabetes Mellitus Mouse Models

Maintaining the homeostasis of metal elements is essential for enhancing insulin function and mitigating the risk of diabetic complications. However, the interactions between metal dysregulation and biological macromolecules remain poorly understood, representing a critical knowledge gap that necessitates further investigation. Here, we conducted integrative omics analyses encompassing metallome, proteome, and metabolome in diabetic mouse models to explore their intricate interplay. Compared with healthy control kidneys, we identified 5 metals, 1032 proteins, and 289 metabolites that were significantly altered in type I diabetes mellitus (T1DM), while 4 metals, 1037 proteins, and 340 metabolites were differentially expressed in type II diabetes mellitus (T2DM). Significant changes in diabetes-associated elements, such as vanadium (V) and manganese (Mn), across diverse organs underscore the critical role of metals in disease onset and progression. Integrated multi-omics analysis uncovers substantial correlations between diabetes-associated metals, proteins or metabolites, such as a significant negative correlation between V and branched-chain-amino-acid aminotransferase, cytosolic BCAT1 protein in T1DM and a positive correlation between zinc (Zn) and hypotaurine in T2DM. The multi-layer molecular landscape constructed in this study provides analytical strategies for dissecting the molecular mechanisms underlying diabetes, and establishes experimental evidence to support the clinical translation of metallome-targeted precision interventions for diabetic patients.