Mo-Rubbing abdominal improves metabolic homeostasis in type 2 diabetes mellitus mice via a jejunum-specific GLP1-dependent mechanism.

AIMS: Type 2 diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by chronic hyperglycaemia and insulin resistance. Although pharmacological therapies such as glucagon-like peptide 1 (GLP1) receptor agonists are effective, issues including side effects and cost limit their long-term use. Mo-Rubbing abdominal, a non-pharmacological traditional technique, has shown potential in improving metabolic health, but its efficacy and underlying mechanisms in T2DM remain unclear. This study aimed to systematically evaluate the therapeutic effects of Mo-Rubbing abdominal on glucose and lipid metabolism and to explore whether its mechanisms involve the GLP1-GLP1 receptor (GLP1R)-insulin receptor substrate 1 (IRS1)/AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signalling pathway. MATERIALS AND METHODS: A T2DM mouse model was established using a high-fat diet. Mice were divided into control, T2DM model, liraglutide-treated, and Mo-Rubbing abdominal-treated groups. Systemic metabolic parameters, including body weight, blood glucose, lipid profiles, and insulin sensitivity, were assessed. Histopathological changes in the liver and jejunum were evaluated via H&E staining. Bulk RNA sequencing was performed on jejunal and hepatic tissues to identify differentially expressed genes. Key proteins and genes in the GLP1-related pathway were examined using ELISA, qRT-PCR, Western blot, and immunohistochemistry. RESULTS: Mo-Rubbing abdominal significantly improved body weight, glucose tolerance, and insulin sensitivity in T2DM mice, with effects comparable or superior to liraglutide. Serum levels of haemoglobin A1C (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, and cholesterol were markedly restored. RNA-seq revealed that jejunal tissues exhibited pronounced transcriptional responses to Mo-Rubbing abdominal, with enrichment in pathways related to metabolism, circadian rhythm, and endoplasmic reticulum stress. Mo-Rubbing abdominal enhanced GLP1 and GLP1R expression in the jejunum and upregulated downstream effectors IRS1 and AMPK, while downregulating mTOR. Additionally, Mo-Rubbing abdominal-regulated genes were associated with reduced risk of colorectal and liver cancers. CONCLUSION: Mo-Rubbing abdominal effectively ameliorates T2DM symptoms and systemic metabolic dysregulation by activating the GLP1-GLP1R-IRS1/AMPK/mTOR pathway, particularly in the jejunum. These findings support Mo-Rubbing abdominal as a promising non-pharmacological intervention for T2DM, with potential benefits for preventing diabetes-associated complications.