电针通过mTORC1/S6K1通路对胰岛素抵抗模型大鼠中枢胰岛素信号转导相关蛋白的影响

IF 1.3 4区 医学 Q4 INTEGRATIVE & COMPLEMENTARY MEDICINE
Xiu-feng GU (顾秀锋) , Jing-zhi WANG (王静芝) , Ming KONG (孔茗) , Li CHEN (陈丽) , Jie SONG (宋杰) , Tao QU (瞿涛)
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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 (<em>S</em>+EA), <span>l</span>-leucine (L), and <span>l</span>-leucine + EA (<em>L</em>+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 <em>S</em>+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.</div></div><div><h3>Results</h3><div>(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 (<em>P</em> &lt; 0.05, <em>P</em> &lt; 0.01). (2) Compared to the M group, the EA and <em>S</em>+EA groups showed reduced body weight, FBG, GSK-3β, mTORC1, and S6K1 phosphorylation, with increased GIR, IRS-1, Akt phosphorylation, and mRNA expression (<em>P</em> &lt; 0.05, <em>P</em> &lt; 0.01). 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引用次数: 0

摘要

目的探讨电针(EA)对胰岛素抵抗(IR)大鼠下丘脑胰岛素信号转导相关蛋白表达及磷酸化的影响。方法选用Wistar大鼠75只。10只大鼠随机分为正常组(N)。将50只成功造模的大鼠随机分为模型组(M)、EA组、假EA组(S+EA)、L -亮氨酸组(L)和L -亮氨酸+EA组(L+EA),每组10只。取“观园穴”(CV 4)、“中脘穴”(CV 12)、“足三里穴”(ST 36)、“凤龙穴”(ST 40),每周3次,每次10分钟,连用8周。S+EA组针刺深度≤2mm,无电刺激,疗程相同,取穴相同。测量体重、空腹血糖(FBG)和胰岛素敏感性(葡萄糖输注率,GIR)。Western blot分析胰岛素受体底物-1(IRS-1)、(蛋白激酶B)Akt、糖原合成酶激酶3β(GSK-3β)、雷帕霉素复合物1的机制靶点(mTORC1)和核糖体S6激酶1(S6K1)及其磷酸化形式。PCR检测IRS-1、Akt、GSK-3β mRNA的表达。结果(1)与N组相比,M组大鼠体重、FBG增加,GSK-3β、mTORC1和S6K1磷酸化水平升高,GIR、IRS-1、Akt磷酸化水平和mRNA表达水平降低(P <;0.05, P <;0.01)。(2)与M组相比,EA和S+EA组小鼠体重、FBG、GSK-3β、mTORC1和S6K1磷酸化水平降低,GIR、IRS-1、Akt磷酸化水平和mRNA表达水平升高(P <;0.05, P <;0.01)。(3)与EA组相比,S+EA组大鼠体重、GSK-3β磷酸化、mRNA表达增加,P - irs -1和P - akt表达降低(P <;0.05);L和L+EA组GSK-3β、mTORC1和S6K1磷酸化升高,GIR、IRS-1和Akt mRNA表达降低(P <;0.05)。(4)与L+EA组相比,L组GSK-3β、mTORC1和S6K1磷酸化水平较高,GIR、Akt mRNA和P -Akt表达水平较低(P <;0.05, P <;0.01)。结论ea对IR大鼠的体重、糖脂代谢和胰岛素敏感性有积极影响,对中枢胰岛素信号转导相关蛋白有调节作用,可能与其抑制下丘脑mTORC1/S6K1通路活性有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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 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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来源期刊
World Journal of Acupuncture-Moxibustion
World Journal of Acupuncture-Moxibustion INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
1.30
自引率
28.60%
发文量
1089
审稿时长
50 days
期刊介绍: The focus of the journal includes, but is not confined to, clinical research, summaries of clinical experiences, experimental research and clinical reports on needling techniques, moxibustion techniques, acupuncture analgesia and acupuncture anesthesia.
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