Acupuncture, Endocrine Inflammation, and Metabolic Regulation

The endocrine system is highly interconnected. Hormones from different glands interact with one another, so endocrine diseases often present with complex, multisystem symptoms. These conditions may involve abnormal metabolism of carbohydrates, proteins, fats, water, electrolytes, and purines.

A growing body of research indicates that chronic, low-grade, non-specific inflammation is closely related to the onset and progression of type 2 diabetes and obesity, and plays a key role in their complications.

1. PI3K/Akt Signaling, Insulin Sensitivity, and Electroacupuncture

The PI3K/Akt signaling pathway is a core insulin signal transduction pathway. It regulates glucose metabolism, protein synthesis, inflammatory responses, and vascular homeostasis. In a high-fat diet–induced type 2 diabetes model, electroacupuncture (EA) at PC6, ST36, SP6, and BL23 has been shown to:

• Inhibit excessive weight gain in diabetic rats
• Activate the PI3K/Akt pathway
• Inhibit adhesion cascades and harmful vascular inflammation
• Regulate eNOS expression in endothelial cells and support vascular function
• Influence the structural integrity of pancreatic β cells
• Improve insulin sensitivity and insulin secretion

These findings suggest that acupuncture can act on insulin signaling upstream and downstream, integrating metabolic and vascular anti-inflammatory effects.

2. Epigenetic Regulation: Sirt1, Histone Deacetylation, and Macrophage Polarization

Histone acetylation is an important epigenetic mechanism that regulates macrophage function. EA at ST36, ST40, CV3, and CV4 has been reported to:

• Stimulate Sirt1, a histone deacetylase
• Promote Sirt1-dependent H3K9 histone deacetylation in white adipocytes
• Down-regulate M1-type peritoneal macrophage expression
• Inhibit the NF-κB signaling pathway
• Reduce TNF-α and relieve chronic low-grade inflammation caused by diet-induced obesity (DIO)
• Improve insulin sensitivity, glucose tolerance, and lower blood lipid levels

This indicates that acupuncture can regulate metabolic inflammation not only through cytokine changes but also via epigenetic mechanisms.

3. Adipose Tissue Inflammation, Adipokines, and Electroacupuncture

Adipose tissue is an active endocrine organ. In obesity, excessive macrophage infiltration into adipose tissue drives chronic inflammation and insulin resistance. EA at CV12 and CV4 has been shown to:

• Inhibit macrophage proliferation and/or infiltration into adipose tissue
• Promote a more favorable, anti-inflammatory adipokine balance
• Adjust the adiponectin/leptin ratio
• Improve insulin sensitivity and lower blood glucose

4. Acupuncture for Diabetic Complications

Long-term hyperglycemia damages both large and small blood vessels and contributes to cardiac, gastrointestinal, and peripheral nerve complications. Acupuncture has been studied in several of these conditions.

(1) Diabetic Cardiomyopathy (DCM)

Manual acupuncture (MA) at PC6 and ST36 has been shown to:

• Reduce blood glucose
• Up-regulate IGF1R and restore AMP-activated protein kinase (AMPK) activity, a key regulator of energy metabolism
• Inhibit NLRP3 inflammasome activation
• Down-regulate IL-1α, IL-1β, IL-6, IL-8, TNF-α, ICAM-1, and MCP-1 in myocardial tissue and blood
• Improve myocardial remodeling, systolic and diastolic function

(2) Diabetic Gastroparesis

Diabetic gastroparesis is mainly related to damage of interstitial cells of Cajal (ICCs), the pacemaker cells of gastrointestinal motility. HO-1, expressed by ICCs, is an inducible heme oxygenase that participates in anti-inflammatory and antioxidant responses.

EA at ST36:

• Promotes HO-1–positive M2 macrophage expression
• Reduces M1 macrophage expression
• Up-regulates IL-10
• Reverses pathological changes in ICCs and protects the ICC network in gastric tissue
• Relieves dyspepsia symptoms and promotes gastric emptying

(3) Diabetic Peripheral Neuropathy (DPN)

DPN arises from chronic sensory and motor nerve damage caused by hyperglycemia and metabolic disorders. MA at BL13, BL20, and BL23:

• Inhibits activation of spinal microglia
• Reduces TNF-α, IL-1β, and IL-6
• Improves peripheral nerve function

5. Role of ST36 and Overall Endocrine Modulation

Across endocrine diseases such as diabetes, obesity, and diabetic complications, ST36 is the most frequently used acupuncture point. Evidence suggests that acupuncture at ST36 has a reliable therapeutic effect on DCM, diabetic gastroparesis, and DPN.

Both low-frequency and high-frequency EA at ST36 can promote gastric emptying in rats, indicating that stimulation frequency is not the main determinant of efficacy for diabetic gastroparesis.

Overall, acupuncture can regulate PI3K/Akt and NF-κB signaling, modulate inflammatory cytokine production, and exert regulatory effects on endocrine glands and hormone secretion. However, the precise mechanisms of these endocrine effects still require further investigation.

內分泌腺與荷爾蒙之間彼此緊密串連， 因此內分泌系統疾病往往呈現多器官、多系統、症狀複雜的臨床樣貌， 牽涉到醣類、蛋白質、脂肪、水分、電解質與普林等多種代謝異常。

越來越多研究指出，慢性、隱匿且低度的發炎狀態，與第二型糖尿病的發生與惡化 有密切關聯，也與肥胖與多種糖尿病併發症息息相關。

一、PI3K/Akt 訊號、胰島素敏感度與電針調節

PI3K/Akt 訊號通路是胰島素作用的關鍵路徑之一， 負責調控葡萄糖代謝、蛋白質合成、血管內皮穩定與發炎反應。

在高脂飲食誘發的第二型糖尿病大鼠模型中， 施以電針 PC6、ST36、SP6、BL23 可：

• 抑制體重持續上升
• 啟動 PI3K/Akt 胰島素訊號
• 抑制血管黏附級聯反應與有害的血管發炎
• 調節血管內皮細胞中的 eNOS 表達，維持血管功能
• 影響胰島 β 細胞結構與功能
• 改善胰島素敏感度與胰島素分泌

二、表觀遺傳調控：Sirt1、組蛋白去乙醯化與巨噬細胞極化

組蛋白乙醯化是調控巨噬細胞發炎反應的重要表觀遺傳機制。 研究顯示，電針於 ST36、ST40、CV3、CV4 可：

• 啟動Sirt1（具去乙醯化酶活性）
• 促進白色脂肪細胞中 H3K9 組蛋白去乙醯化
• 下調M1 型腹腔巨噬細胞表達
• 抑制 NF-κB 訊號路徑
• 降低 TNF-α，緩解飲食性肥胖（DIO）所造成的慢性低度發炎
• 改善胰島素敏感度、葡萄糖耐受並降低血脂

三、脂肪組織發炎、脂肪激素平衡與電針

脂肪組織本身是一個內分泌器官。在肥胖狀態下，過多的巨噬細胞浸潤脂肪組織， 會促進慢性發炎並加重胰島素阻抗。

電針於 CV12、CV4 可：

• 抑制巨噬細胞在脂肪組織中的增殖與／或浸潤
• 促進較為抗發炎的脂肪激素分佈
• 調整adiponectin/leptin 比值
• 改善胰島素敏感性並降低血糖

四、針灸在糖尿病併發症中的應用

長期高血糖會損傷大小血管，導致心臟、胃腸與周邊神經等多系統併發症。 針灸在其中幾項疾病已有較多研究。

（1）糖尿病性心肌病變（DCM）

以手針 PC6、ST36 為主的治療，可：

• 降低血糖
• 上調 IGF1R，恢復 AMPK（能量代謝關鍵分子）活性
• 抑制 NLRP3 發炎小體的啟動
• 下調心肌與血液中的 IL-1α、IL-1β、IL-6、IL-8、TNF-α、ICAM-1、MCP-1
• 改善心肌重塑，提升收縮與舒張功能

（2）糖尿病性胃排空障礙（diabetic gastroparesis）

在糖尿病性胃排空障礙中，ICC（Cajal 間質細胞）的損傷是胃排空延遲的主因之一。 ICC 表達的 HO-1 是一種可誘導型血基質氧合酶，參與抗發炎與抗氧化反應。

電針 ST36 可：

• 增加 HO-1 陽性 M2 巨噬細胞表達
• 降低 M1 巨噬細胞
• 上調IL-10
• 逆轉胃組織中 ICC 的病理變化，保護 ICC 網絡
• 改善消化不良症狀，促進胃排空

（3）糖尿病周邊神經病變（DPN）

DPN 主要來自高血糖與代謝失衡導致的感覺與運動神經慢性損傷。 針刺 BL13、BL20、BL23 可：

• 抑制脊髓小膠質細胞的活化
• 降低 TNF-α、IL-1β、IL-6
• 改善周邊神經功能

五、足三里（ST36）的核心角色與整體內分泌調節

在糖尿病、肥胖與其併發症（如 DCM、胃排空障礙、DPN）等內分泌相關疾病中， 足三里（ST36） 是使用頻率最高、效果最被證實的穴位之一。

研究也顯示，對 ST36 施以低頻與高頻電針皆能促進胃排空， 暗示在糖尿病性胃排空障礙中，刺激頻率並非決定療效的唯一關鍵因素。

整體而言，針灸可透過調節 PI3K/Akt、NF-κB 等訊號路徑， 影響發炎細胞激素的產生，並對胰島與廣泛分布於各器官中的內分泌細胞及荷爾蒙傳導 產生良性調節作用。然而，針灸對內分泌系統的完整作用機制，仍有待進一步釐清。