Potential Therapeutic Targets for Type 2 Diabetes: A Multi-Center Data Analysis Based on Proteomics

Background Despite the advent of numerous pharmacological agents designed to enhance the management of type 2 diabetes, treating this condition continues to pose significant challenges. Consequently, this study aims to identify potential therapeutic targets for type 2 diabetes through Mendelian randomization(MR). Methods This research primarily utilizes publicly accessible data from extensive genome-wide association studies and protein quantitative trait locus studies. The study predominantly adopts an MR framework to estimate the causal effects of specific proteins on the risk of developing type 2 diabetes. To corroborate the findings, multiple validation methodologies are employed, including summary data-based Mendelian randomization (SMR), external validation cohorts, bayesian colocalization analysis, single-cell analysis, protein-protein interaction (PPI) networks, pathways derived from KEGG 2021 Human and DsigDB. Results Our study identifies 25 proteins potentially associated with the risk of type 2 diabetes. SMR and external validation affirmed that 14 proteins, including ARG1, PAM, WWOX, and SHBG, may function as viable therapeutic targets for type 2 diabetes. Single-cell analysis illuminated the expression patterns of six proteins predominantly in pancreatic islets. Colocalization analysis and PPI networks elucidated the potential roles of these proteins in the pathogenesis of type 2 diabetes. The KEGG 2021 Human database indicated that the glycan degradation pathway may mediate the effects of MANBA and HEXB on the development of type 2 diabetes. DsigDB identified 41 potential therapeutic drugs for the treatment of type 2 diabetes. Conclusion These findings provide novel insights and directions for drug development aimed at the prevention and treatment of type 2 diabetes.