Electroacupuncture at ST36 Restores Glucose Homeostasis in Prediabetes Mice by Modulating Pancreatic β-Cell Function

The global prevalence of prediabetes is rising, posing a significant risk for progression to type 2 diabetes mellitus (T2DM) and associated complications. Current interventions often involve lifestyle modifications, but effective non-pharmacological strategies are needed, especially for individuals at high risk. Pancreatic β-cell dysfunction and endoplasmic reticulum (ER) stress are central to prediabetes pathogenesis, leading to impaired insulin secretion and glucose intolerance. Electroacupuncture (EA) at specific acupoints like "Zusanli" (ST36) has shown promise in metabolic regulation, offering a potential therapeutic avenue by targeting these underlying mechanisms.

Researchers conducted three distinct experiments using C57BL/6J mice to model acute hyperglycemia (AH), low-risk prediabetes (LRP), and high-risk prediabetes (HRP). Each experiment included normal, model, and EA groups. For AH, mice received an intraperitoneal injection of 2 g/kg glucose solution, followed by a single 20-min session of EA at bilateral ST36 (1 mA, 10 Hz). LRP mice were fed a high-fat diet for 1 week, receiving EA daily for 4 days starting on day 4. HRP mice were fed a high-fat diet for 8 weeks, with EA applied 3 times a week for 12 total sessions starting at 4 weeks. Blood glucose and glucose tolerance were measured, and serum HbA1c, insulin, and glucagon levels were quantified by ELISA. Pancreatic morphology was assessed via HE staining, while expression of ATF6, ERN1, EIF2AK3, p21, M2-AchR, M3-AchR, and PDX-1 in β-cells was determined by Western blot and qPCR.

Electroacupuncture (EA) at ST36 significantly improved blood glucose homeostasis across all three prediabetes models (AH, LRP, HRP). It effectively restored glucose tolerance and normalized serum levels of glycated hemoglobin A1c (HbA1c), insulin, and glucagon in the treated groups. Pancreatic morphology, assessed by HE staining, also showed improvements, suggesting a protective effect on β-cell structure. The study specifically found that EA modulated key markers of pancreatic β-cell function and endoplasmic reticulum (ER) stress pathways.

EA intervention regulated the expression levels of activating transcription factor 6 (ATF6), endoplasmic reticulum to nucleus signaling 1 (ERN1), eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3), p21 (a cell cycle factor), muscarinic acetylcholine receptor M2 (M2-AchR), M3-AchR, and pancreatic and duodenal homeobox factor-1 (PDX-1) within pancreatic β-cells. These findings indicate a multi-faceted mechanism involving the ER stress response, cell cycle regulation, and cholinergic signaling in restoring β-cell function and glucose control.