Electroacupuncture in glycemic control: Transitioning from clinical controversies to potential basic research

Table 1 Major animal models and corresponding acupoint selection in electroacupuncture for hypoglycemic research

Model name	Number of published articles in WoS and PubMed (from the database to the present)	Number of published electroacupuncture articles in WoS and PubMed	Acupoints	Major references	Ref.
HFD + STZ; T2DM	15200	68	Tianshu (ST25) (88%), Zusanli (ST36)	Hypoglycemic effect of electroacupuncture	[3]
Diabetic (db/db) mice	8300	52	Yishu (EX-B3) (79%), Zusanli (ST36) (76%)	Electroacupuncture at Yishu (EX-B3) promotes β-cell regeneration via modulating pancreatic innervation in type 2 diabetic db/db mice	[26]

HFD: High-fat diet; STZ: Streptozotocin; T2DM: Type 2 diabetes mellitus.

Table 2 Main stimulation parameters and corresponding acupoints in electroacupuncture for hypoglycemic research

Stimulation frequency and current intensity	Waveform	Acupoints	Treatment duration	Ref.
2 Hz, 1 mA	Continuous	Zusanli (ST36)	20 minutes/session, once daily for 4 weeks	[30]
2 Hz, 1 mA	Continuous	Zhongwan (CV12), Zusanli (ST36), Guanyuan (CV4), Fenglong (ST40)	15 minutes/session, every other day for 8 weeks	[26]
10 Hz, 2 mA	Continuous	Zhongwan (CV12)	30 minutes/session, every other day for 3 weeks	[3]
15 Hz, 1-2 mA	Continuous	Zusanli (ST36), Zhongwan (CV12)	20-30 minutes/session, once daily for 4 weeks	[12]
2-10 Hz, 1.5-2 mA, 100 Hz, 3 mA	Sparse-dense wave, interrupted wave	Tianshu (ST25), Zusanli (ST36), Shenshu (BL23)	30 minutes/session, every other day for 3 weeks	[3]
10 Hz, 1-3 mA	Sparse-dense wave	Tianshu (ST25)	30 minutes/session, once daily for 2 weeks	[2]

Table 3 Types of animals used in electroacupuncture for hypoglycemic research

Species	Diabetic state	Acupoints (bilateral or unilateral)	Frequency (Hz)	Duration	Current (mA)	Effect description	Mechanism research conclusion	Ref.
Rat	Type 1 diabetes (fasted)	Zusanli (ST36) (ST36, bilateral)	15	30-60 minutes	-	Reduces fasting blood sugar	Activates vagus nerve-liver axis: Enhances parasympathetic activity, promotes glycogen synthesis in liver and inhibits gluconeogenesis	[31]
	Type 1 diabetes (STZ induced)	Zusanli (ST36) (ST36, bilateral)	15	30/60 minutes	-	Enhances insulin signaling protein expression, significantly lowers blood sugar	Modulates IRS-1/AKT pathway: Stimulates vagus nerve to release acetylcholine, activating insulin signaling pathways in skeletal muscle and liver	[32]
	Type 2 diabetes (fasted)	Zusanli (ST36) (ST36, bilateral)	2	20 minutes	1	Reduces blood sugar	Inhibits hypothalamic inflammation: Modulates HPA axis, reduces corticosterone levels, alleviates inflammation and improves insulin resistance	[33]
	Type 2 diabetes (HFD + low-dose STZ induced)	Zusanli (ST36), Pishu (BL20), bilateral	15	30 minutes per session, once per day for 14 days	1	Significantly improves insulin sensitivity	Reshapes gut microbiota: Increases SCFA-producing bacteria, reduces LPS levels, alleviates systemic inflammation, improves insulin sensitivity	[25]
Mouse	Normal (fasted)	Zusanli (ST36), bilateral	15	30 minutes	-	Reduces blood sugar	Activates cholinergic anti-inflammatory pathway: Enhances vagus nerve activity, inhibits splenic TNF-α release, reduces inflammation	[24]
	Type 2 diabetes (HFD)	Guanyuan (CV4) + Zhongwan (CV12), bilateral	3	30 minutes	-	Significantly lowers postprandial blood sugar	Activates cholinergic anti-inflammatory pathway: Enhances vagus nerve activity, inhibits splenic TNF-α release, reduces inflammation	[34]
	Type 2 diabetes (STZ induced)	Zusanli (ST36), bilateral	10	30 minutes per day, for 8 weeks	1-3	Lowers random blood sugar and fasting blood sugar	Promotes β-cell regeneration: Modulates PINS, activates β-cell proliferation signals (e.g., PDX-1), inhibits pancreatic fibrosis	[2]

HPA: Hypothalamic-pituitary-adrenal; SCFA: Short-chain fatty acid; LPS: Lipopolysaccharide; TNF-α: Tumor necrosis factor alpha; PINS: Pancreatic intrinsic nerves; HFD: High-fat diet; IRS: Insulin receptor substrate; STZ: Streptozotocin.

Table 4 Classification of main mechanisms in electroacupuncture for hypoglycemic research

Specific mechanism	Supporting evidence	Relevant acupoints	Experimental subjects	Ref.
HPA axis regulation	Reduces adrenal corticosteroids (such as cortisol), improves endocrine disorders	Yishu (EX-B3)	T2DM rats	[3]
Anti-inflammatory pathway	Inhibits NLRP3 inflammasome activation, reduces IL-1β, improves chronic inflammation	Non-specific	STZ-induced diabetic rats, HFD high-fat diet mice, db/db genetically diabetic mice, OLETF obese diabetic rats	[12]
Neurobiological mechanism	Enhances parasympathetic nerve (e.g., vagus nerve) activity, improves local circulation and glucose consumption	Zhongwan (CV12), Tianshu (ST25), etc.	OLETF rats	[38]
Gut microbiota and inflammation control	Increases SCFAs, reduces circulating LPS levels, lowers systemic inflammation	Zhongwan (CV12), Tianshu (ST25), Zusanli (ST36)	T2DM model	[26]
Insulin signaling pathway activation	Activates PI3K/Akt pathway, enhances GLUT2 and GCK mRNA expression, reduces fasting insulin levels	Zusanli (ST36), Shenshu (BL23)	T2DM rats	[3]
ta-VNS	Stimulates auricular vagus nerve via projections from the vagus nerve (ABVN) to the NTS, affects the concentration changes of the neurotransmitters noradrenaline, GABA and ACh in the central nervous system	Non-specific	Humans, SD rats	[39,40]

LPS: Lipopolysaccharide; ACh: Acetylcholine; GABA: Γ-aminobutyric acid; NTS: Nucleus tractus solitaries; ta-VNS: Transcutaneous auricular vagus nerve stimulation; HPA: Hypothalamic-pituitary-adrenal; SCFA: Short-chain fatty acid; HFD: High-fat diet; STZ: Streptozotocin; IL: Interleukin; GLUT2: Glucose transporter 2; GCK: Glucokinase; NTS: Nucleus tractus solitaries; SD rats: Sprague-Dawley rats.