Abstract

circRNAs are involved in diabetes mellitus pathogenesis. Electroacupuncture (EA) is an effective therapeutic strategy for diabetes mellitus. However, whether the mechanism of action of EA on diabetes mellitus is related to altered circRNAs is unclear. The aim of this study was to reveal the effect of EA on circRNA expression in plasma exosomes and the underlying signaling pathway in mice with type 2 diabetes mellitus (T2DM). In total, 10 mice were randomly categorized into a normal group and 20 mice were used for the T2DM model preparation and randomly divided into the model and model + EA groups. Mice in the model + EA group were administered EA treatment. Changes in the fasting blood glucose (FBG) level and islet structure were evaluated. Plasma exosomes were subjected to RNA sequencing, and then bioinformatics analysis and real-time quantitative PCR (qPCR) verification were performed. EA treatment reduced the FBG level, preserved the islet structure, and reduced the islet β cell apoptotic rate in T2DM mice. After EA treatment, 165 differentially expressed circRNAs were found. GO and KEGG analyses revealed that thyroid hormone signaling was actively regulated by EA. circRNA/miRNA interaction analysis revealed mmu-mir-7092-3p to be closely associated with circINPP4B, suggesting that the phosphatidylinositol signaling pathway may be affected by EA. qPCR confirmed that 12 circRNAs had significant differences. These findings suggested that EA intervention can significantly protect islet function and improve the FBG level in T2DM, possibly via regulation of thyroid hormone and phosphatidylinositol signaling.

Highlights

  • Diabetes mellitus is a chronic endocrine disorder caused by lifestyle changes or inadequate insulin secretion due to hereditary factors, islet dysfunction, or development of insulin resistance

  • In a statement issued by the American Diabetes Association (ADA) in 2005, acupuncture therapy was suggested to be effective for neuralgia at any stage of type 2 diabetes [12, 13]

  • All male C57BL/6 mice were fed with basic forage for one week for adaptation. en, 10 mice were categorized according to their body weight into the normal (N) group. e remaining 20 mice were prepared as the type 2 diabetes mellitus (T2DM) model by feeding with high-forage diets consisting of casein 22.8%, dextrin 17%, DL-methionine 0.2%, minerals 4%, sodium bicarbonate 10.5%, vitamins 1%, heavy tartaric acid choline 0.2%, sucrose 17.5%, soybean oil 2.5%, hydrogenated coconut oil 33.35%, and potassium citrate 0.4%

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Summary

Introduction

Diabetes mellitus is a chronic endocrine disorder caused by lifestyle changes or inadequate insulin secretion due to hereditary factors, islet dysfunction, or development of insulin resistance. It often has some serious complications such as diabetic nephropathy, diabetic ophthalmopathy, and pathological changes in the cardiovascular system and can endanger human life and health [1]. Acupuncture is reported to promote weight loss [10, 11]. In a statement issued by the American Diabetes Association (ADA) in 2005, acupuncture therapy was suggested to be effective for neuralgia at any stage of type 2 diabetes [12, 13]. In a single-blind experiment, acupuncture was found to significantly alleviate diabetic

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