Identifying potential therapeutic targets of Tang-Yi-Ping for the treatment of impaired glucose tolerance: a tandem mass tag-labeled quantitative proteomic analysis

BACKGROUND: This study uses the tandem mass tag (TMT)-labeled quantitative proteomic analysis to identify potential therapeutic protein targets of a Chinese prescription called Tang-Yi-Ping (TYP) for the treatment of impaired glucose tolerance (IGT) in rats. METHODS: A total of 31 specific-pathogen free (SPF) male Wistar rats were used in our study. Ten were randomly selected as a control group, while 21 received a high-sugar and high-fat diet combined with an intraperitoneal injection of streptozotocin to establish IGT subjects. After eliminating 2 rats without successful modeling, 19 were randomly divided into a TYP group (n=9) and IGT model group (n=10). The TYP group was given a TYP decoction of 6.36 mg/kg−1/d−1. After 8 weeks of intervention, blood glucose-related indicators were measured, and cell morphology was observed by hematoxylin and eosin (HE) staining. TMT-labeled proteomic analysis was applied to detect the differentially expressed proteins (DEPs) in the pancreases of the three groups. The intersection of the DEPs in both the TYP group and IGT model group underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify the related biological functions and signal transduction pathways. Finally, western blot (WB) was used to verify the TMT proteomics results. RESULTS: TYP can effectively reduce blood glucose and improve islet morphology in IGT rats. We identified a total of 16 potential therapeutic protein targets of TYP, 4 of which were upregulated, while 12 were downregulated, including Rbp4, Fam3b, Flot2, etc. [fold change (FC) >1.1, P<0.05]. The significant signal transduction pathways included arginine and proline metabolism, glyceride metabolism, glycerophospholipid metabolism, mTOR, Wnt, and insulin signaling pathways. CONCLUSIONS: For anti-IGT therapy, we found TYP regulates 16 protein targets, multiple biological functions, and multiple signal transduction pathways. This study thus makes a significant contribution to identifying new potential therapeutic targets for treating IGT.