Electroacupuncture modulates the gut-brain axis via the PI3K/Akt pathway to improve feeding behavior, body weight, glucolipid metabolism, and reduce insulin resistance in T2DM rats

Background: The rising prevalence and high mortality of diabetes have made it a significant public health concern. This study explores how electroacupuncture (EA) influences the PI3K/Akt pathway and its role in regulating the gut-brain axis, focusing on whether EA can modulate this axis via the PI3K/Akt pathway in the treatment of type 2 diabetes mellitus (T2DM). The research aims to reveal the mechanisms underlying EA's therapeutic effects and to investigate a novel strategy for managing T2DM.

Methods: To induce T2DM in rat models, a high-fat diet and intraperitoneal injection of streptozotocin (STZ) were used. The rats were then randomly divided into four groups: a T2DM group, an EA group, an EA plus PI3K Inhibitor group (EA + LY294002), and a control group (Con), which received a standard diet and a citric acid-sodium citrate solution. Following five weeks of intervention, assessments were conducted for food intake, body weight, fasting blood glucose (FBG), blood lipid profiles, and Insulin resistance (IR). To analyze the PI3K/Akt pathway and gut-brain axis indices, various methods were employed, including Western blotting, qPCR, immunohistochemistry staining, HE staining, and 16 S rRNA Sequencing.

Results: Our research shows that EA improves food intake, body weight, FBG, lipid levels (TC, TG, HDL, LDL), serum Insulin levels, IR and Insulin sensitivity indices in T2DM rats. Additionally, EA boosts the expression of colonic tight junction proteins ZO-1, Occludin, and Claudin-1 while reducing intestinal inflammation and intestinal cell Apoptosis. It also regulates Ghrelin and PYY levels in both colonic and hypothalamic tissues, improving the gut microbiota structure. These effects can be reversed by PI3K inhibitors.

Conclusions: EA plays a role in managing feeding behavior, body weight, and glucolipid metabolism, as well as alleviating IR in T2DM rats. EA may contribute to the preservation of intestinal mucosal barrier integrity, likely through anti-inflammatory and anti-apoptotic actions mediated by the PI3K/Akt pathway. Additionally, EA appears to influence the regulation of brain-gut peptides and promote a healthier gut microbiota composition. These findings suggest that EA holds potential as an therapeutic approach for T2DM, with its mechanisms potentially linked to the modulation of the gut-brain axis via the PI3K/Akt pathway. Further research is warranted to fully elucidate these effects and their clinical implications.

Electroacupuncture; Gut-brain axis; PI3K/Akt pathway; Type 2diabetes mellitus.