50-PUB: Research on the Effect of an Antidiabetic Herbal Formula by Restoring the Islet Microenvironment and Cellular Function in Type 2 Diabetes Mellitus

Introduction and Objective: The disorder of islet microenvironment is a core feature in the occurrence and development of type 2 diabetes mellitus (T2DM), in which the homeostasis imbalance between macrophages and β cells is considered as an early key event. This study aims to explore the mechanism of a clinically effective antidiabetic herbal formula for treating T2DM in the islet microenvironment, with a focus on the regulatory effects on macrophage polarization and β-cell function. Methods: Dynamic changes in fasting blood glucose and key indicators of islet function were observed in the T2DM mouse model, along with pathological alterations in the pancreas. Changes in islet β-cells and macrophages were assessed by immunofluorescence. Furthermore, single-cell sequencing was performed. Results: Experiments confirmed that this formula could significantly reduce blood sugar levels, improve islet function, and repair pathological tissues. It could also increase β-cell cells and raise the proportion of M2 subtype macrophages in the islet microenvironment. Single-cell sequencing results also indicated that the formula enhances β-cell expression and promotes the conversion of macrophages to anti-inflammatory M2 type, while identifying significant differential genes in both cell types. Further enrichment analysis suggested that it might exert biological effects on energy metabolism, immune regulation, protein homeostasis, and related signaling pathways in macrophages. Simultaneously, it impacted crucial biological processes involving β-cell function and proliferation. Conclusion: This study demonstrates that this antidiabetic herbal formula can exert therapeutic effects on T2DM by regulating islet microenvironment, promoting the transformation of macrophages into anti-inflammatory M2 type, and enhancing the function and quantity of β cells. Future research will further focus on the specific regulatory mechanisms of cell communication and signal networks within the islet microenvironment. Disclosure Y. Lin: None. L. Han: None. L. Zhang: None. R. Wu: None. Funding Guang'anmen Hospital South Campus, China Academy of Chinese Medical Sciences (Y2024-20); the National Natural Science Foundation of China (82104840)