Electroacupuncture at ST25 combined with metformin improves intestinal function via the JAK/STAT pathway in a rat model of diabetes

Background: Metformin (Met) is a first-line pharmacological treatment for type 2 diabetes mellitus (T2DM). The potential effect of combining electroacupuncture (EA) at ST25 ( Tianshu ) with Met in ameliorating intestinal injury remains largely unexplored. Methods: We established wild-type (Control) and diabetic model groups that remained untreated (Model), received EA only (EA), received Met treatment only (Met) or received EA combined with Met (EA + Met), and compared markers of intestinal injury and insulin resistance, as well as effects on signal transducer and activator of transcription (STAT) proteins and microRNAs. Results: EA and Met treatment (alone and in combination) had positive effects on fasting plasma glucose, fasting insulin levels, Homeostatic Model Assessment–insulin resistance (HOMA-IR) indices and stool number, while fecal water content was positively impacted by EA treatment (with or without concurrent Met) but not Met alone. Hematoxylin-eosin staining demonstrated that both EA alone and EA in combination with Met appeared to repair intestinal damage in the jejunum, ileum and colon. In addition, enzyme-linked immunosorbent assay revealed that serum interleukin 10 levels were restored in all treatment groups. Furthermore, quantitative real-time polymerase chain reaction (PCR) analysis revealed that EA at ST25 resulted in the activation of STAT5A in the jejunum, as well as STAT5A , STAT5B and STAT6 in the ileum. Notably, in the EA + Met group, there was a specific enhancement of STAT2 , STAT3 and STAT5B in the colon, indicating segment-specific activation within distinct regions of the intestine. Conclusion: EA at ST25 may ameliorate intestinal injury via the Janus kinase (Jak)/STAT signaling pathway and is closely related to jejunal and ileal segments. These findings provide a theoretical basis for EA combined with medication.