Effects of electroacupuncture on central insulin signal transduction-related proteins in insulin resistance model rats via the mTORC1/S6K1 pathway

Objective: To investigate the effects of electroacupuncture (EA) on the expression and phosphorylation of insulin signal transduction-related proteins in the hypothalamus of insulin resistance (IR) rats. Methods: There were totally seventy-five Wistar rats. Ten rats were randomly assigned to the Nor...

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Main Authors: Xiu-feng GU, Jing-zhi WANG, Ming KONG, Li CHEN, Jie SONG, Tao QU
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-07-01
Series:World Journal of Acupuncture - Moxibustion
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Online Access:http://www.sciencedirect.com/science/article/pii/S1003525725000467
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author Xiu-feng GU
Jing-zhi WANG
Ming KONG
Li CHEN
Jie SONG
Tao QU
author_facet Xiu-feng GU
Jing-zhi WANG
Ming KONG
Li CHEN
Jie SONG
Tao QU
author_sort Xiu-feng GU
collection DOAJ
description Objective: To investigate the effects of electroacupuncture (EA) on the expression and phosphorylation of insulin signal transduction-related proteins in the hypothalamus of insulin resistance (IR) rats. Methods: There were totally seventy-five Wistar rats. Ten rats were randomly assigned to the Normal group (N).The remaining 65 rats were fed a high-fat diet, fifty successfully modeled rats were randomly divided into the Model (M), EA, Sham EA (S+EA), l-leucine (L), and l-leucine + EA (L+EA) groups, with 10 rats in each group.EA was applied at acupoints “Guanyuan (CV 4)”, “Zhongwan (CV 12)”, “Zusanli (ST 36)”, and “Fenglong (ST 40)”, with each session lasting 10 min, three times per week for 8 weeks. The S+EA group received needle insertion to a depth of ≤2 mm without electrical stimulation, with the same treatment duration and same acupoint selection. Body weight, fasting blood glucose (FBG), and insulin sensitivity (glucose infusion rate, GIR) were measured. Western blot analysis was used to assess insulin receptor substrate-1(IRS-1) , (Protein kinase B)Akt, glycogen synthase kinase-3β(GSK-3β),mechanistic target of rapamycin complex 1(mTORC1), and Ribosomal S6 kinase 1(S6K1), along with their phosphorylated forms. PCR was used to evaluate mRNA expression of IRS-1, Akt, and GSK-3β. Immunofluorescence was used to detect hypothalamic Akt localization. Results: (1) Compared to the N group, the M group exhibited increased body weight, FBG, and phosphorylation of GSK-3β, mTORC1, and S6K1, with decreased GIR, IRS-1, Akt phosphorylation, and mRNA expression (P < 0.05, P < 0.01). (2) Compared to the M group, the EA and S+EA groups showed reduced body weight, FBG, GSK-3β, mTORC1, and S6K1 phosphorylation, with increased GIR, IRS-1, Akt phosphorylation, and mRNA expression (P < 0.05, P < 0.01). (3) Compared to the EA group, the S+EA group had higher body weight, GSK-3β phosphorylation, and mRNA expression, with reduced p-IRS-1 and p-Akt expression (P < 0.05); the L and L+EA groups showed increased GSK-3β, mTORC1, and S6K1 phosphorylation, with decreased GIR, IRS-1, and Akt mRNA expression (P < 0.05). (4) Compared to the L+EA group, the L group exhibited higher GSK-3β, mTORC1, and S6K1 phosphorylation, with lower GIR, Akt mRNA, and p-Akt expression (P < 0.05, P < 0.01). Conclusion: EA positively influences body weight, glucose-lipid metabolism, and insulin sensitivity in IR rats, with regulatory effects on central insulin signal transduction-related proteins, potentially linked to its suppression of hypothalamic mTORC1/S6K1 pathway activity.
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spelling doaj-art-fd60e66f4fb849a18ad9f531565eebce2025-08-20T04:02:31ZengKeAi Communications Co., Ltd.World Journal of Acupuncture - Moxibustion1003-52572025-07-0135326226810.1016/j.wjam.2025.06.007Effects of electroacupuncture on central insulin signal transduction-related proteins in insulin resistance model rats via the mTORC1/S6K1 pathwayXiu-feng GU0Jing-zhi WANG1Ming KONG2Li CHEN3Jie SONG4Tao QU5Hubei University of Chinese Medicine Wuhan 430061, China (湖北中医药大学, 武汉 430061, 中国)Hubei University of Chinese Medicine Wuhan 430061, China (湖北中医药大学, 武汉 430061, 中国); College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine Wuhan 430061, China (湖北中医药大学针灸骨伤学院, 武汉 430061, 中国); Hubei Shizhen Laboratory Wuhan 430061, China (湖北时珍实验室, 武汉 430061, 中国); Hubei Collaborative Innovation Center for Acupuncture and Moxibustion in Disease Prevention and Treatment Wuhan 430061, China (针灸治未病湖北省协同创新中心, 武汉 430061, 中国); Corresponding author.Hubei University of Chinese Medicine Wuhan 430061, China (湖北中医药大学, 武汉 430061, 中国); College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine Wuhan 430061, China (湖北中医药大学针灸骨伤学院, 武汉 430061, 中国)Hubei University of Chinese Medicine Wuhan 430061, China (湖北中医药大学, 武汉 430061, 中国); College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine Wuhan 430061, China (湖北中医药大学针灸骨伤学院, 武汉 430061, 中国); Hubei Shizhen Laboratory Wuhan 430061, China (湖北时珍实验室, 武汉 430061, 中国); Hubei Collaborative Innovation Center for Acupuncture and Moxibustion in Disease Prevention and Treatment Wuhan 430061, China (针灸治未病湖北省协同创新中心, 武汉 430061, 中国)Hubei University of Chinese Medicine Wuhan 430061, China (湖北中医药大学, 武汉 430061, 中国)Hubei University of Chinese Medicine Wuhan 430061, China (湖北中医药大学, 武汉 430061, 中国); College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine Wuhan 430061, China (湖北中医药大学针灸骨伤学院, 武汉 430061, 中国)Objective: To investigate the effects of electroacupuncture (EA) on the expression and phosphorylation of insulin signal transduction-related proteins in the hypothalamus of insulin resistance (IR) rats. Methods: There were totally seventy-five Wistar rats. Ten rats were randomly assigned to the Normal group (N).The remaining 65 rats were fed a high-fat diet, fifty successfully modeled rats were randomly divided into the Model (M), EA, Sham EA (S+EA), l-leucine (L), and l-leucine + EA (L+EA) groups, with 10 rats in each group.EA was applied at acupoints “Guanyuan (CV 4)”, “Zhongwan (CV 12)”, “Zusanli (ST 36)”, and “Fenglong (ST 40)”, with each session lasting 10 min, three times per week for 8 weeks. The S+EA group received needle insertion to a depth of ≤2 mm without electrical stimulation, with the same treatment duration and same acupoint selection. Body weight, fasting blood glucose (FBG), and insulin sensitivity (glucose infusion rate, GIR) were measured. Western blot analysis was used to assess insulin receptor substrate-1(IRS-1) , (Protein kinase B)Akt, glycogen synthase kinase-3β(GSK-3β),mechanistic target of rapamycin complex 1(mTORC1), and Ribosomal S6 kinase 1(S6K1), along with their phosphorylated forms. PCR was used to evaluate mRNA expression of IRS-1, Akt, and GSK-3β. Immunofluorescence was used to detect hypothalamic Akt localization. Results: (1) Compared to the N group, the M group exhibited increased body weight, FBG, and phosphorylation of GSK-3β, mTORC1, and S6K1, with decreased GIR, IRS-1, Akt phosphorylation, and mRNA expression (P < 0.05, P < 0.01). (2) Compared to the M group, the EA and S+EA groups showed reduced body weight, FBG, GSK-3β, mTORC1, and S6K1 phosphorylation, with increased GIR, IRS-1, Akt phosphorylation, and mRNA expression (P < 0.05, P < 0.01). (3) Compared to the EA group, the S+EA group had higher body weight, GSK-3β phosphorylation, and mRNA expression, with reduced p-IRS-1 and p-Akt expression (P < 0.05); the L and L+EA groups showed increased GSK-3β, mTORC1, and S6K1 phosphorylation, with decreased GIR, IRS-1, and Akt mRNA expression (P < 0.05). (4) Compared to the L+EA group, the L group exhibited higher GSK-3β, mTORC1, and S6K1 phosphorylation, with lower GIR, Akt mRNA, and p-Akt expression (P < 0.05, P < 0.01). Conclusion: EA positively influences body weight, glucose-lipid metabolism, and insulin sensitivity in IR rats, with regulatory effects on central insulin signal transduction-related proteins, potentially linked to its suppression of hypothalamic mTORC1/S6K1 pathway activity.http://www.sciencedirect.com/science/article/pii/S1003525725000467ElectroacupunctureInsulin resistanceHypothalamusMtorc1/s6k1 pathway
spellingShingle Xiu-feng GU
Jing-zhi WANG
Ming KONG
Li CHEN
Jie SONG
Tao QU
Effects of electroacupuncture on central insulin signal transduction-related proteins in insulin resistance model rats via the mTORC1/S6K1 pathway
World Journal of Acupuncture - Moxibustion
Electroacupuncture
Insulin resistance
Hypothalamus
Mtorc1/s6k1 pathway
title Effects of electroacupuncture on central insulin signal transduction-related proteins in insulin resistance model rats via the mTORC1/S6K1 pathway
title_full Effects of electroacupuncture on central insulin signal transduction-related proteins in insulin resistance model rats via the mTORC1/S6K1 pathway
title_fullStr Effects of electroacupuncture on central insulin signal transduction-related proteins in insulin resistance model rats via the mTORC1/S6K1 pathway
title_full_unstemmed Effects of electroacupuncture on central insulin signal transduction-related proteins in insulin resistance model rats via the mTORC1/S6K1 pathway
title_short Effects of electroacupuncture on central insulin signal transduction-related proteins in insulin resistance model rats via the mTORC1/S6K1 pathway
title_sort effects of electroacupuncture on central insulin signal transduction related proteins in insulin resistance model rats via the mtorc1 s6k1 pathway
topic Electroacupuncture
Insulin resistance
Hypothalamus
Mtorc1/s6k1 pathway
url http://www.sciencedirect.com/science/article/pii/S1003525725000467
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