电针减轻2型糖尿病大鼠胰岛素抵抗,影响下丘脑IRS-1/PI3K/AKT通路和miRNA-29a-3p

IF 2.4 3区 医学 Q2 INTEGRATIVE & COMPLEMENTARY MEDICINE
Acupuncture in Medicine Pub Date : 2025-04-01 Epub Date: 2025-03-21 DOI:10.1177/09645284251327205
Shuting Zhuang, Shaoyang Liu, Rui Li, Haoru Duan
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引用次数: 0

摘要

摘要目的:本研究旨在通过检测下丘脑miRNA-29a-3p、胰岛素受体底物(IRS)-1 /磷脂酰肌醇3-激酶(PI3K) /蛋白激酶B (AKT) /信号换能器和转录激活因子(STAT)3通路以及代谢分子如proopiomanocortin (POMC)、神经肽Y (NPY)和针刺相关蛋白(AgRP),探讨电针(EA)对2型糖尿病(T2DM)大鼠模型的影响。目的是揭示EA减轻T2DM的分子机制。方法:采用高脂饮食暴露后注射链脲佐菌素(STZ)诱导T2DM,并给予PI3K抑制剂LY294002,观察EA是否通过下丘脑IRS-1/PI3K/AKT通路介导。将36只大鼠分为模型组、EA组和EA + LY294002组,每组12只。另外12只大鼠作为健康对照组。测定各组大鼠的食物摄取量、体重、空腹血糖(FBG)、胰岛素、总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白(LDL)水平。采用定量聚合酶链反应(qPCR)检测下丘脑micro (mi)RNA-29a-3p的表达,采用Western blotting、qPCR和免疫组织化学分析胰岛素受体信号通路中间体和代谢分子。结果:EA干预后,T2DM大鼠的食物摄取量和体重均明显下降。此外,血清FBG、胰岛素、TC、TG和LDL浓度均有降低。胰岛素抵抗的稳态模型评估(HOMA-IR)指数也显著下降。EA显著降低下丘脑miRNA-29a-3p表达,增强IRS-1/PI3K/AKT/STAT3通路活性,同时调节POMC、NPY和AgRP表达。这些作用至少部分被LY294002逆转,这支持了我们的假设,即EA通过下丘脑IRS-1/PI3K/AKT通路减轻T2DM。结论:EA可能通过激活IRS-1/PI3K/AKT/STAT3通路,调节POMC、NPY和AgRP,改善下丘脑IR,从而减少食物摄入,纠正代谢失衡,缓解T2DM。EA对IRS-1/PI3K/AKT通路的影响可能与miRNA-29a-3p下调有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Electroacupuncture alleviates insulin resistance and impacts the hypothalamic IRS-1/PI3K/AKT pathway and miRNA-29a-3p in a rat model of type 2 diabetes.

Objective: This study aimed to explore the effects of electroacupuncture (EA) in a rat model of type 2 diabetes mellitus (T2DM) by examining the hypothalamic miRNA-29a-3p, insulin receptor substrate (IRS)-1 / phosphatidylinositol 3-kinase (PI3K) / protein kinase B (AKT) / signal transducer and activator of transcription (STAT)3 pathway, as well as metabolic molecules including proopiomelanocortin (POMC), neuropeptide Y (NPY) and agouti-related protein (AgRP), with the goal of revealing the molecular mechanisms by which EA mitigates T2DM.

Methods: T2DM was induced by high-fat diet exposure followed by streptozotocin (STZ) injection, and LY294002 (a PI3K inhibitor) was administered to evaluate whether the effects of EA were mediated through the hypothalamic IRS-1/PI3K/AKT pathway. T2DM was induced in 36 rats that were assigned to model, EA and EA + LY294002 groups (n = 12 each). An additional 12 rats formed a healthy control group. Food intake, body weight and serum levels of fasting blood glucose (FBG), insulin, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) were measured. Hypothalamic micro (mi)RNA-29a-3p expression was detected by quantitative polymerase chain reaction (qPCR), while insulin receptor signaling pathway intermediates and metabolic molecules were analyzed using Western blotting, qPCR and immunohistochemistry.

Results: After the EA intervention, T2DM rats showed a significant decrease in both food intake and body weight. In addition, there were reductions in serum concentrations of FBG, insulin, TC, TG and LDL. The homeostatic model assessment of insulin resistance (HOMA-IR) index also significantly declined. EA significantly decreased hypothalamic miRNA-29a-3p expression and enhanced IRS-1/PI3K/AKT/STAT3 pathway activity, while regulating POMC, NPY and AgRP expression. These effects of EA were at least partially reversed by LY294002 administration, which supports our hypothesis that EA mitigates T2DM via the hypothalamic IRS-1/PI3K/AKT pathway.

Conclusion: EA may improve hypothalamic IR by activating the IRS-1/PI3K/AKT/STAT3 pathway and regulating POMC, NPY and AgRP, thereby reducing food intake, correcting metabolic imbalance and mitigating T2DM. The effect of EA on the IRS-1/PI3K/AKT pathway may involve miRNA-29a-3p downregulation.

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来源期刊
Acupuncture in Medicine
Acupuncture in Medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
4.70
自引率
4.00%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Acupuncture in Medicine aims to promote the scientific understanding of acupuncture and related treatments by publishing scientific investigations of their effectiveness and modes of action as well as articles on their use in health services and clinical practice. Acupuncture in Medicine uses the Western understanding of neurophysiology and anatomy to interpret the effects of acupuncture.
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