Hindawi

BioMed Research International

Volume 2018, Article ID 3128378, 9 pages
https://doi.org/10.1155/2018/3128378

Review Article
Acupoint Therapy on Diabetes Mellitus and Its Common
Chronic Complications: A Review of Its Mechanisms

Yiyi Feng, Yuchen Fang, Yiqin Wang , and Yiming Hao

Shanghai Key Laboratory of Health Identification and Assessment/Laboratory of TCM Four Diagnostic Information,
Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

Correspondence should be addressed to Yiming Hao; hymjj888@163.com

Received 25 May 2018; Revised 22 September 2018; Accepted 8 October 2018; Published 22 October 2018

Academic Editor: Swaran J. S. Flora

Copyright © 2018 Yiyi Feng et al. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Acupoint therapy is one of the therapeutic means in Traditional Chinese Medicine (TCM) concerning acupoints and meridians,
including manual acupuncture, electroacupuncture, moxibustion, external application, acupoint injection, and catgut embedding.
In the treatment of diabetes and its common chronic complications, acupoint therapy has proved to have specific curative effect and
notable advantages. Single or combined with western medicine, it has superior efficacy and less side effects than western medicine
alone. Studying its mechanism can provide experimental basis for clinical treatment. Relevant researches in the recent 5 years
mainly focused on the mechanism of electroacupuncture, point injection, catgut embedding, etc. in the treatment of diabetes and
common diabetic complications such as neuropathy, nephropathy, and hepatopathy. The possible theories involve the regulation
of nerve conduction, signal pathways, hormone level, protein expression, oxidative stress level, structure restoration, etc. The most
studied acupoints are Zusanli (ST36), Shenshu (BL23), Sanyinjiao (SP6), Yishu (EX-B3), and Zhongwan (CV12). However, most
of the studies have been based on diabetes model rats rather than clinical trials. Moreover, the mechanism of acupoint therapy
treating other chronic complications like diabetic retinopathy and that of other effective methods like pressing ear with beans,
auricular points plaster therapy, and external application remain unclear. Therefore, this aspect still awaits further research.

1. Introduction combined with Western medicine, it has more superior effi-

cacy and less side effects than Western medicine alone. Many
Diabetes mellitus (DM) is a ubiquitous metabolic disease researches have shown that methods like electroacupuncture,
which severely threatens the health and even the survival of acupoint injection, and catgut embedding can effectively
humankind. Chronic hyperglycaemia is very likely to result in decrease blood glucose, enhance insulin sensitivity, allevi-
vascular damage, which will lead to a series of diabetic com- ate symptoms of various complications, and even prevent
plications in heart, liver, stomach, kidney, muscle, peripheral diabetes in specific populations [2]. Studying its mechanism
nerve, etc. According to Global Report on Diabetes [1], dia- will be conducive to its clinical application, thus benefiting
betic complications may cause heart attack, stroke, blindness, diabetic patients worldwide. Our study reviewed relevant
renal failure, and lower limb amputation which have deadly researches in the recent 5 years regarding the latest progress
consequences; in 2012, DM alone brought about the death of the mechanism study of acupoint therapy in the treatment
of 1.5 million patients while its complications devitalized of DM and its common chronic complications. Currently,
another 2.2 million patients. Acupoint therapy of Traditional most of the studies are experiments on streptozotocin- (STZ-)
Chinese Medicine (TCM) may be a way out. It is one of induced Type 2 Diabetes Mellitus (T2DM) model rats.
the therapeutic means in TCM concerning acupoints and
meridians, including manual acupuncture, electroacupunc- 2. The Mechanism Study of Hyperglycaemia
ture, moxibustion, external application, acupoint injection, Acupoint Treatment
and catgut embedding. Acupoint therapy has proved to
have specific curative effect and notable advantages in the Hyperglycaemia, which resulted from insulin secretion dys-
treatment of DM and its chronic complications. Single or function or impairment of insulin biological function, is
2 BioMed Research International

one of the most fundamental characteristics of diabetes activity of another subunit p110 and realizes the functions of
mellitus. Acupoint therapy has been repeatedly confirmed insulin. However, exceedingly expressed p85𝛼 competitively
to have evident effects on decreasing blood glucose. The inhibit the binding of p85-p110 and its downstream molecule
existing studies have found that the regulation of related IRS-1 so that the function of PI3K is suppressed. A study
nerve excitement, protein expression, and signaling pathways found that electroacupuncture at Zusanli (ST36) and Quchi
that strengthens insulin sensitivity plays an important role in (LI11) decreases the expression of PI3K-p85 to ameliorate
the treatment. the insulin resistance of model rats [8]. A more explicit
The endocrine system and the nervous system coregulate research has shown that electroacupuncture at Neiguan
the metabolic activities in our bodies and they influence each (PC6), Zusanli (ST36), Sanyinjiao (SP6), and Shenshu (BL23)
other significantly. Yishu (EX-B3) is located below the 8th restores the level of insulin signaling related molecules like
spinous process of thoracic vertebrae, where there is part IRS-1, IRS-2, Akt2, aPKC𝜁, and GLUT4 to normal and
of T8 that innervates the pancreas. Electroacupuncture on reversed the increased PI3K-p85𝛼 level [9]. In this way,
T2DM rats at point Yishu (EX-B3) helps to reduce blood metabolic activities like glycogen synthesis are improved via
glucose and protect the shape of islets, which is consistent PI3K/Akt signaling pathway. In addition, the improvement of
with the theory of innervation of neural segment [3]. The insulin resistance can reverse the pathological changes of vas-
theory describes the neural connection between body surface cular endothelium. Vascular endothelial dysfunction is the
and internal organs. The main functions of a certain acupoint pathological basis and early stages of atherosclerosis, which
are focused on the organs innervated by neural system is inseparable and forms a vicious cycle with the occurrence
adjacent to the acupoint. As long as a group of acupoints of insulin resistance [10]. It turns out to be another result
are located in the same neural segment, their functions are of PI3K/Akt signalling pathway regulation. Researchers have
similar to each other even if they are not from the same studied the effect of electroacupuncture at Shenshu (BL23),
meridian [4]. Obviously, the regulation of Yishu (EX-B3) Neiguan (PC6), Zusanli (ST36), and Sanyinjiao (SP6) on
on the pancreas is conformable to this theory. Besides, the T2DM rats which demonstrates an increase in the expression
hypothalamic-pituitary-adrenal axis (HPA), as an important of IRS-1, PI3K, Akt2, and eNOS in vascular endothelium. This
part of neuro-endocrine system, also exerts influence on signal transduction pathway is the downstream of insulin
the insulin secretion. Electroacupuncture at Yishu (EX-B3) in vascular endothelium cells. When insulin sensitivity is
is demonstrated to decrease the level of adrenal cortical enhanced, the signalling pathway can be better activated
hormone (CORT) and reduce HPA hyperfunction, thus and promote the production of NO. In this way, vascular
ameliorating endocrine dyscrasia and improving physical as endothelial dysfunction is mitigated, and vasodilation can
well as psychological health status of rats to some extent [5]. exert positive counteraction on glucose utilization [11].
Another important initial factor of T2DM is insulin
resistance. One of the characteristic indexes of insulin resis- 3. The Mechanism Study of Diabetic
tance is high fasting insulin (FINS) level due to the patients’ Neuropathy Acupoint Treatment
poor insulin sensitivity and low efficiency of uptaking and
utilizing glucose. Electroacupuncture at Zusanli (ST36) and Diabetic neuropathy is a kind of peripheral or central
Shenshu (BL23) is reported to reduce the level of FINS neuropathy caused by diabetic metabolic disturbance and
and protect islet B cell morphology by enhancing mRNA angiopathy. The percent of complicated neuropathy ranges
expression of GLUT2 and GCK [6]. GLUT2 is an efficient from 60% to 80% and its mortality rate reaches 20% in ten
carrier for glucose and GCK is an enzyme that facilitates years from its occurrence [12]. It includes a wide variety of
phosphorylation of glucose, both of which function together diseases and acupoint therapy interferes them in different
as “glucose sensor” and respond to fluctuations of glu- mechanisms as follows.
cose level. Enhancement of them leads to improvement of
insulin sensitivity and ameliorate insulin resistance. Manual 3.1. Diabetic Peripheral Neuropathy (DPN). The incidence
acupuncture on Quchi (LI11), Hegu (LI4), Zusanli (ST36), of peripheral neuropathy in T2DM patients reached more
Xuehai (SP10), Fenglong (ST40), Yinlingquan (SP9), Diji than 60% and among them only approximately 53% of DPN
(SP8), Sanyinjiao (SP6), and Taichong (LR3) with “spleen- patients survive after 3 years of its occurence [13, 14]. It
stomach harmonizing” technique can also reduce insulin may decrease sensory nerve conduction velocity (SNCV)
resistance. “Spleen-stomach harmonizing” technique is cre- and impair sensation or movement. Acupoint therapy can
ated by Doctor Zhang Zhilong with a series of operations on effectively increase SNCV and alleviate subjective symptoms.
the acupoints mentioned mainly for curing Type 2 diabetes The mechanism involves upregulating the positive factors
mellitus and its complications. The study shows it possibly and downregulating the negative ones. For instance, elec-
reduces insulin resistance by increasing the gene expression troacupuncture and acupoint injection with mecobalamin
level of IRS-1, IRS-2, and GLUT4 in muscular tissue which at Zusanli (ST36) and Shenshu (BL23) are demonstrated
suggests an activation of the signal transduction pathway to increase the expression of nerve growth factor (NGF)
of the phosphatidylinositol 3-kinase (PI3K)/Akt [7]. More and its receptor TrkA [15]. Likewise, catgut implantation at
studies have confirmed the effect of electroacupuncture on Pishu (BL20), Shenshu (BL23), and Zusanli (ST36) combined
the PI3K/Akt signal transduction pathway. In this pathway, with taking herbal remedy, TCM prescription “Tangtong
the activity of PI3K of insulin resistant rats is usually inhib- drink,” enhances the content of NGF plus lower that of
ited. Normally, its regulatory subunit p85 adjusts the catalytic serum transforming growth factor-𝛽1 (TGF-𝛽1) [16]. They
BioMed Research International 3

both promote the regeneration of nerves and repair of nerve ameliorate vascular endothelial dysfunction as mentioned.
injuries. Other positive regulative factors that are reported AT II, on the other hand, play its role by binding with
to be raised by acupuncture or acupoint injection includes AT I receptor and AT II receptor, the former of which is
superoxide dismutase (SOD) expression [17], content of nitric found increased in gastric tissue of DGP rats. Likewise,
oxide (NO) in the serum [18]. SOD is an important antioxi- IGF-1 and its receptor are found significantly higher in
dant defense of living cells exposed to oxygen and can have DGP rats so the cut-down of them might suggest an action
positive effect on alleviating cell damage. Low-level of NO, as mechanism of electroacupuncture [28–30]. As a matter of
previously mentioned, is related to vascular endothelium dys- fact, the restoration of Cajal interstitial cells, mediation of
function that can lead to nerve hypoxia and ischemia. What hormones, and nervous system supplement each other. With
is more, NO is an important inhibitory neurotransmitter and the treatment of needling at specific points, the amount
the lack of it can cause disorders of neural functions. The of Cajal interstitial cells increases and gastric slow wave is
increase of these molecules apparently exerts benign effects regulated, thus alleviating gastric myoelectric arrhythmias,
on neuropathy patients. On the contrary, researchers who promoting signal transduction between nervous system and
treated DPN patients with salvia injections at Zusanli (ST36) smooth muscle, and eventually normalizing gastric motor
combined with lipoid acid intravenous injection found that [31]. However, there still remain some mysteries unsolved.
the expression of high-sensitivity C-reactive protein (hs- Researchers have paid attention to the modulation of ghrelin
CRP) and the content of malondialdehyde (MDA) were and its role in strengthening gastric motility. Some con-
significantly decreased [17]. Another similar study on low- cluded that electroapuncture at Zusanli, Liangmen (ST21),
frequent electroacupuncture at Zhongwan (CV12), Mingmen and Sanyinjiao (SP6) contributes to an increase in ghrelin
(DU4), and Zusanli (ST36) combined with mecobalamin and growth hormone secretagogue receptor (GHSR) mRNA
injection has shown the same result of reducing hs-CRP while another group had a contradictive result under the
as well as homocysteine (Hcy) [19]. High level of hs-CRP, similar experimental conditions that the level of ghrelin
MDA, and Hcy mentioned above is correlated to causing mRNA declines after the treatment [32–35]. Whether it
or aggravating neuropathy, so their decrease protects the is because of human error or an undiscovered underlying
structure of neurons. mechanism needs further investigation. One conjecture of
Another common DPN is diabetic gastroparesis. This our group is that some unknown factors made the pathology
disease usually results from vagus nerve lesion, which mainly of diabetic gastroparesis of the model rats in two groups
manifests as delayed gastric emptying, decreased gastroin- different. One decreases the ghrelin while the other increases
testinal motility and weakened gastric electrical activity with it. Acupuncture played a mediative role, respectively, in
an incidence of 50%-76% [20]. Recent studies have focused both cases and had the tendency to balance the body
on the interstitial cells of Cajal (ICCs) in the gastric antrum, status.
gastrointestinal nervous system and hormones, etc. [21]
Firstly, it was observed that the ultrastructure of ICCs and its 3.2. Diabetic Cardiac Autonomic Neuropathy. Diabetic car-
pacing function was restored, and cell apoptosis remarkably diac autonomic neuropathy is the damage of structure or
reduced after the treatment of electroacupuncture at points functions of cardiac autonomic nerves due to chronic hyper-
of Zusanli (ST36) and Zhongwan (CV12). This is possibly glycaemia. In a research studying the therapeutic effect of
concerned with the upregulation of stem cell factors (SCF) electroacupuncture at Feishu (BL13), Xinshu (BL15), Yishu
mRNA and neuronal nitric oxide synthase (nNOS) mRNA (EX-B3), Pishu (BL20), Neiguan (PC6), Quchi (LI11), Zusanli
by mSCF/KIT-ETV1 signaling pathway [22–26]. Secondly, (ST36), and Sanyinjiao (SP6), the inhibition of NGF excessive
related hormones as important regulators of gastrointestinal expression was observed and the content of ChAT, CNTF, and
functions and motility are affected directly or indirectly. For GAP-43 raised strikingly, the latter three of which participate
example, the levels of motilin, a gastrointestinal motility in the restoration of nervous injuries [36].
enhancer, and gastrin, the high-level of which has inhibitory NGF has the biological functions of nutrition and growth
effect on gastric movement, are obviously elevated in gas- promotion of nerves. It is essential in maintaining nor-
troparesis patients. The secretion of them will be inhibited mal growth and development of nerves, but its excessive
by abdominal acupuncture at Zhongwan (CV12), Xiawan expression may lead to abnormal proliferation of neurons.
(RN10), Qihai (BL24), Guanyuan (BL26), Tianshu (ST25), As discussed above, we know that NGF has low expression
Daheng (SP15), Huaroumen (ST24), and Wailing (ST26), in the patients with diabetic peripheral neuropathy, and
as well as point injection of Vitamin B12 or mecobalamin their NGF increases after electroacupuncture. An experiment
at Zusanli (ST36), the effect of which is superior to using of rats has also proved that NGF can promote peripheral
western medicine like mosapride alone [20, 27]. Studies nerve regeneration [37]. But on the contrary, NGF is high
of electroacupuncture at Zusanli (ST36), Liangmen (ST21), in diabetic cardiac autonomic neuropathy which is caused
and Sanyinjiao (SP6) also revealed a growth in endothelial by the endogenous NGF produced in myocardium for the
nitric oxide synthase (eNOS) mRNA, insulin, and its receptor maintenance of neural integrity in several heart tissues. This
(IR), as well as a cut-down on AT II mRNA, insulin-like finding in a dog experiment also pointed out that exogenously
growth factor-1 (IGF-1), and its receptor (IGF-1 R) in the infused NGF can also protect against neural stunning of sym-
gastric antrum. Among these molecules, the binding of pathetic cardiac innervation [38]. And the electroacupunc-
insulin and IR protects ICCs and the expression of eNOS ture may have played the role of exogenous NGF in depress-
mRNA can lead to more abundant content of NO which can ing the excessive expression of endogenous NGF. The specific
4 BioMed Research International

mechanisms of the effect of electroacupuncture treatment on 4. The Mechanism Study of Diabetic

this disease need to be further studied. Nephropathy Acupoint Treatment
3.3. Diabetic Foot. A diabetic foot exhibits ulcers or gan- Diabetic Nephropathy (DN) is glomerular sclerosis led
grenes resulted from lower limb microcirculation disorder by glucose metabolism disorders, accompanied by pathog-
led by diabetic neuropathy and vascular structural damage. nomonic symptoms like abnormal urinal protein. DN is
6-Keto-PGF1𝛼 and thromboxane B2 (TXB2 ) are one of the one of the most common microvascular complications of
most common and effective biochemical factors of regulating diabetes, with an incidence of 20%-40% [42]. It is also one
thrombosis balance, and pathological changes might break of the major causes of death for diabetic patients. Diabetic
the balance and cause various disorders of blood circulation. nephropathy is reversible at early stages, so prompt therapy
Researchers discovered that Vitamin B1 injection at point may help injured kidney recover. We collected the mecha-
Jiexi (ST41) increases the content of 6-Keto-PGF1𝛼 and nism study of acupoint injection, catgut implantation com-
decreases that of TXB2 to maintain the original balance in bined with Chinese medicine, and “spleen-stomach harmo-
grade 0 diabetic foot patients. They reckoned that the acu- nizing” needling. These therapeutic means affect the structure
point injection boosts the nutrition supplement of neurons, and functions of kidney through different chemical signals.
restores part of its functions and exert feedback influence Shuxuening injection at Zusanli (ST36), Sanyinjiao (SP6),
on blood circulation. In the progress, specific regulating Fenglong (ST40), Yinlingquan (SP9), and Zhongshu (DU7)
factors of blood circulation like 6-Keto-PGF1𝛼 and TXB2 alternately of DN patients is proved to have certain curative
are affected and regional microcirculation is ameliorated effects. Shuxuening is an extract from ginkgo leaf, which
[39]. contains flavanoids, phenols, alkaloids, etc. The injection
significantly decreases the expression of vascular endothelial
3.4. Diabetic Anterior Horn Injury of Spinal Cord. Diabetic growth factor (VEGF), the rise of which will cause an increase
anterior horn injury of spinal cord is another common in expansion of extracellular matrix and mesangial matrix
nervous lesion. It usually implicates motor neurons of of kidney, and therefore lead to glomerular sclerosis [43].
spinal cord, etc., and brings about muscular atrophy and Catgut implantation at Shenshu (BL23), Huiyang (BL35), and
a decline of muscular tension. A study on diabetic model Guanyuan (BL26) combined with taking TCM prescription
rats demonstrated that the protein expression of apoptosis “Tangtong drink” cuts down the content of TGF-𝛽1 and IGF-1
gene of anterior horn neurons of spinal cord, Bax, was in the serum of DN model rats at early stages [44]. The former
remarkably lowered while its correspondent antiapoptosis one is the crucial cell factor in the mechanism of glomerular
gene Bcl-2 had a substantial increase after the treatment of sclerosis while the latter participates in the alteration of
electroacupuncture at Zusanli (ST36) and Yishu (EX-B3). glomerular hemodynamics, cell hypertrophy, etc. The thera-
As a result, the ratio of Bcl-2 and Bax was upregulated pies both downregulate the harmful growth of particular cell
and was approaching normal standards [40]. This suggests factors and promote the repair of renal structure. The possible
that electroacupuncture can modulate gene expression and ramifications of the regulation are the amelioration of glucose
prevent the apoptosis of neurons. metabolism and renal hemodynamics, the correction of high
filtration and high perfusion status of kidney, the reduction
3.5. Diabetic Myopathy. As mentioned above, neuropathy can of growth and differentiation of renal cells, etc., all of which
lead to myopathy, a complication of great importance but alleviate nephropathy and improve renal functions.
often neglected. The mechanism of low-frequency electrical “Spleen-stomach harmonizing” needling also plays an
stimulation at Yanglingquan (GB34) and Zusanli (ST36) important role in the clinical treatment of DN. Acupuncture
involves a variety of biochemical signals. First, it upregulates at Zhongwan (CV12), Quchi (LI11), Hegu (LI4), Xuehai
IGF-1 signaling pathway and the expression of microRNA (SP10), Zusanli (ST36), and Yinlingquan (SP9) with this
myomiR which is related to muscle regeneration. This is technique efficaciously improves glomerular filtration and
followed by an increase in phosphorylation level of factors reduce urinary albumin excretion rate of DN patients. Spe-
concerning protein synthesis like AKT, FoxO1, mTOR, and cialized study of it also found extensive regulation of the
p70S6. Then, a series of pathological effects in diabetic model patients’ bodies. During their study, a number of genes and
rats are reversed including the reduction of Pax7, MyoD, signaling pathways were investigated. The study mentioned
myogenin, and MHC-emb expression. From the macroscopic 5 signaling ways that are upregulated, including glutathione
view, the ramifications above can be embodied as promoting metabolism, the interactions of cell factor receptors, etc. The
muscle regeneration, strengthening muscular functions and downregulated genes control altogether 40 signaling path-
attenuating myopathy [41]. ways, concerning type 1 diabetes mellitus, PPAR, etc. Among
To summarize, the study of some of nervous disease is them, gene IFNG and the signaling pathways it regulates
very limited. For instance, only grade 0 diabetic foot was concerning T cell receptor (TCR), hypoxia inducible factor-1
studied in the category of diabetic foot but that of far severer (HIF-1), JAK-STAT signaling pathway, TGF-𝛽, etc. stand out.
grade still have urgent needs of research. Nevertheless, the Furthermore, spleen-stomach harmonizing needling inhibits
mechanisms of different kind of neuropathy are concentrated the excessive expression of MCP-1. The combination of these
on gene, mRNA, or protein regulation of neuron growth or effects modulates the amount and activity of T cell subset,
apoptosis. Future studies can draw on ideas and experiences thus restoring lymphocyte injury [45, 46]. Meanwhile, the
of similar nervous diseases and enrich the theories. needling decreases the oxidative stress level of DN patients
BioMed Research International 5

and strengthens the capability of organism to scavenge free 20

18
radicals [47]. All of the above delay or alleviate renal damage. 16
14
5. The Mechanism Study of Diabetic 12
10
Hepatopathy Treatment 8
6
Liver is of great significance to glucose metabolism of human 4
body. Long-term hyperglycaemia may harm the structure 2
0
of liver, thus counter-reflecting on glucose metabolism and

Zhongwan (CV12)

Neiguan (PC6)

Xuehai (SP10)
Zusanli (ST36)

Shenshu (BL23)

Sanyinjiao (SP6)

Yishu (EX-B3)

Quchi (LI11)

Yinlingquan (SP9)

Hegu (LI4)

Fenglong (ST40)

Guanyuan (BL20)
forming a vicious cycle. As diabetic hepatopathy has only
been raising people’s awareness in recent years, the mecha-
nism study of its treatment is still limited. The theories at
present indicate that electroacupuncture at Yishu (EX-B3)
enhances the expression of gene and protein of glucagon-
like peptide-1 (GLP-1) receptor, a glucose-dependent insulin Figure 1: The appearance frequency of most mentioned acupoints
secretion enhancer, in the liver cells as well as decreases ala- in the articles of recent five years.
nine aminatransferase (ALT) and aspartate aminotransferase
(AST), and the biomarkers of liver cell damage, in the serum
[48, 49]. These alterations protect liver cells and ultimately In biology, structures and functions are united and the
ameliorate diabetic hepatopathy. abnormality of functions is usually concerned with structural
damage. The treatment generally regulates some specific
6. Conclusions biochemical factors to influence particular signal pathways,
eventually controlling the apoptosis and proliferation of cells
As the circumstance of diabetes grows increasingly severe and repairing the damaged structure. Sometimes the therapy
all over the world, acupoint therapy, as one of the most has two-way regulation of one specific factor in different
important parts of Chinese medicine, plays an indispensable studies, and we speculate that the therapy is a process of
role in the treatment of diabetes and its complications. balancing the whole body. Different pathology may cause
We listed the function and effect of acupoint therapy on rise or decline of the content of specific factors, and the
DM and its common chronic complications in Table 1. From therapy corrects them to go to the normal status. The studies
what we have collected, the mechanism study of treatment usually focused on a few factors each time, but the therapy
of hyperglycaemia and its common chronic complications actually regulates the entire body. The nervous system, the
like peripheral neuropathy and nephropathy is comparatively endocrine system, the circulation system, etc. collaborate to
elaborate. However, the correspondent studies of diabetic achieve a more harmonious balance in human body. Due
foot, diabetic anterior horn injury of spinal cord, diabetic to the confined studies, it is basically impossible to draw a
myopathy, diabetic hepatopathy, and other complications complete picture of the mechanism currently. Nevertheless,
unmentioned above like diabetic retinopathy are shallow and the present researches have laid the foundation and pointed
rare. For instance, only grade 0 diabetic foot has been studied out the possible directions. Future studies can draw on the
in the category of diabetic foot. The most studied methods experimental design and consideration of past researches,
of acupoint therapy are electroacupuncture, acupoint injec- enrich the existing theories, and explore more on the clinical
tion, catgut implantation, and manual acupuncture (usually trials.
with “spleen-stomach harmonizing” needling technique), but
the mechanism of other effective ways like pressing ear
with beans, auricular points plaster therapy, and external
Conflicts of Interest
application remains unclear. As shown in Figure 1, the most The authors declare that there are no conflicts of interest
studied acupoints are Zusanli (ST36), which is mentioned regarding the publication of this paper.
18 times in all the articles we collected. This is followed
by Shenshu (BL23) (7 times), Sanyinjiao (SP6) (7 times), Authors’ Contributions
Yishu (EX-B3) (4 times), Zhongwan (CV12) (4 times), and
Quchi (LI11) (4 times). The rest of the acupoints are widely Yiyi Feng and Yuchen Fang wrote the whole manuscript text
distributed. Still, the effects of different acupoints as well which was revised by Yiming Hao. Yiming Hao and Yiqin
as different combination of them need more investigations Wang helped in the ideas of study. All authors (Yiyi Feng,
and experiments. Moreover, most of the studies are experi- Yuchen Fang, Yiqin Wang, and Yiming Hao) reviewed the
ments on model rats rather than clinical trials, so whether manuscript. Yiyi Feng and Yuchen Fang contributed equally
the results are consistent with human body awaits further to this study and share first authorship.
research. Whether electroacupuncture can substitute manual
acupuncture is another problem unsolved hitherto. Acknowledgments
The mechanisms concluded involve the regulation of
nerve conduction, signal pathways, hormone level, protein This work was supported by Shanghai Municipal Commis-
expression, oxidative stress level, and structure restoration. sion of Health and Family Planning Project (no. 20164Y0279),
 6

Table 1: The function and effect of acupoint therapy on DM and its common chronic complications.
Disease Experimental object Different acupoints combination Acupoint therapy Function Effect
1. Innervate the pancreas by neural segment 1. Protect the islets
T2DM rats Yishu (EX-B3) Electroacupuncture 2. Reduce hyperfunction of 2. Ameliorate endocrine
hypothalamic-pituitary-adrenal axis dyscrasia
High-level expression of gene GLUT2 and
T2DM rats Zusanli (ST36), Shenshu (BL23) Electroacupuncture GCK Reduce insulin resistance
Quchi (LI11), Hegu (LI4), Zusanli (ST36),
T2DM rats Xuehai (SP10), Fenglong (ST40), Manual acupuncture High-level expression of gene IRS-1, IRS-2,
Diabetes mellitus Yinlingquan (SP9), Diji (SP8), Sanyinjiao and GLUT4
(SP6), Taichong (LR3)
T2DM rats Zusanli (ST36), Quchi (LI11) Electroacupuncture Low-level expression of PI3K-85p Reduce insulin resistance
Otsuka Long-Evans Zusanli (ST36), Shenshu (BL23), Neiguan 1. High-level of IRS-1, IRS-2, Akt2, aPKC𝜁,
Tokushima Fatty (OLETF) (PC6), Sanyinjiao (SP6) Electroacupuncture and GLUT4 Reduce insulin resistance
rats 2. Low-level of PI3K-p85𝛼
Zusanli (ST36), Shenshu (BL23), Neiguan High-level expression of IRS-1, PI3K, Akt2, 1. Reduce insulin resistance
T2DM rats (PC6), Sanyinjiao (SP6) Electroacupuncture and eNOS 2. Ameliorate vascular
endothelial dysfunction
1. Electroacupuncture High-level expression of nerve growth 1. Promote the regeneration of
DPN rats Zusanli (ST36), Shenshu (BL23) 2. Acupoint injection of factor and its receptor TrkA nerves
mecobalamin 2. Repair of nerve injuries
1. Catgut implantation at 1. High-level expression of nerve growth
DPN rats Pishu (BL20), Shenshu (BL23), Zusanli acupoint factor
(ST36) 2. Take Chinese medicine 2. Low-level expression of transforming
growth factor-𝛽1
1. Acupoint injection of salvia 1. Low-level expression of high-sensitivity
injections C-reactive protein Protect the structure of
Chinese DPN patients Zusanli (ST36) 2. Intravenous injection of 2. Low content of malondialdehyde neurons
3. High-level expression of superoxide
lipoid acid dismutase
Diabetic peripheral 1. Electroacupuncture 1. Low-level expression of high-sensitivity
neuropathy (include Chinese DPN patients Zusanli (ST36), Zhongwan (CV12), 2. Acupoint injection of C-reactive protein
diabetic gastroparesis) Mingmen (DU4) mecobalamin 2. Low-level expression of homocysteine
Restore the ultrastructure and
DGP rats Zusanli (ST36), Zhongwan (CV12) Electroacupuncture High-level expression of stem cell factors pacing function of interstitial
and neuronal nitric oxide synthase cells of Cajal in the gastric
antrum
Zhongwan (CV12), Xiawan (RN10), Qihai
(BL24), Guanyuan (BL26), Tianshu (ST25), 1. Abdominal acupuncture Enhance the secretion of motilin and Regulate gastrointestinal
Chinese DGP patients Daheng (SP15), Huaroumen (ST24), and 2. Acupoint injection of gastrin functions and motility
Wailing (ST26) Vitamin B12

Chinese DGP patients Zusanli (ST36) Acupoint injection of

mecobalamin
1. Growth in endothelial nitric oxide
synthase, insulin and its receptor in the 1. Promote the restoration of
DGP rats Zusanli (ST36), Liangmen (ST21), and Electroacupuncture gastric antrum Cajal interstitial cells
Sanyinjiao (SP6) 2. Low content of AT II, insulin-like growth 2. Mediate hormones and
factor-1 and its receptor in the gastric nervous system
antrum
BioMed Research International
 Table 1: Continued.
Disease Experimental object Different acupoints combination Acupoint therapy Function Effect
Feishu (BL13), Xinshu (BL15), Yishu 1. Low-level expression of nerve growth 1. Prohibit abnormal
Diabetic cardiac (EX-B3), Pishu (BL20), Neiguan (PC6), factor proliferation of neurons
autonomic neuropathy DM rats Quchi (LI11), Zusanli (ST36), Sanyinjiao Electroacupuncture 2. High content of ChAT, CNTF, and 2. Restore the injuries of
BioMed Research International

(SP6) GAP-43 nervous

1. Supply the nutrition of
Chinese level 0 diabetic foot Acupoint injection of Vitamin 1. High content of 6-Keto-PGF1𝛼 neurons
Diabetic foot patients Jiexi (ST41) B1 2. Low content of thromboxane B2 2. Ameliorate the
regionalmicrocirculation of
foot
Diabetic anterior horn DM rats Zusanli (ST36), Yishu (EX-B3) Electroacupuncture 1. High-level expression of gene Bcl-2 Prevent the apoptosis of
injury of spinal cord 2. Low-level expression of gene Bax neurons
1. Up-regulates IGF-1 signaling pathway
2. High-level expression of gene myomiR 1. Promote the muscle
3. Increase in phosphorylation level of regeneration
Diabetic myopathy DM rats Yanglingquan (GB34) and Zusanli (ST36) Electroacupuncture factors concerning protein synthesis like 2. Strengthen the muscular
AKT, FoxO1, mTOR, and p70S6 functions
4. Low-level expression of Pax7, MyoD, 3. Attenuating the myopathy
myogenin and MHC-emb
Acupoint injection of 1. Ameliorate the expansion of
Zusanli (ST36), Sanyinjiao (SP6), Fenglong Shuxuening (extract from extracellular matrix and
Chinese DN patients (ST40), Yinlingquan (SP9), and Zhongshu gingko leaf that contains Low-level expression of vascular mesangial matrix of kidney
(DU7) flavanoids, phenols, alkaloids, endothelial growth factor 2. Ameliorate glomerular
etc.) sclerosis
1. Ameliorate the glucose
metabolism and renal
Shenshu (BL23), Huiyang (BL35), 1. Catgut implantation at Low content of transforming growth hemodynamics
Diabetic nephropathy DN rats acupoint 2. Correct high filtration and
Guanyuan (BL26) 2. Take Chinese medicine factor-𝛽1 and insulin-like growth factor-1 high perfusion status of kidney
3. Reduce growth and
differentiation of renal cells
1. Improve glomerular
1. Regulate gene IFNG, T cell receptor, filtration and reduce urinary
hypoxia inducible factor-1, JAK-STAT albumin excretion rate
Zhongwan (CV12), Quchi (LI11), Hegu signaling pathway, TGF-𝛽, etc.
Chinese DN patients (LI4), Xuehai (SP10), Zusanli (ST36), Manual Acupuncture 2. Modulate the amount and
2. Low-level expression of MCP-1 activity of T cell subset and
Yinlingquan (SP9) 3. Enhance the activity of superoxide restore lymphocyte injury
dismutase 3. Improve the level of
anti-oxidative stress
1. High-level expression of gene and protein
Diabetic hepatopathy DM rats Yishu (EX-B3) Electroacupuncture of glucagon-like peptide-1 receptor
2. Low content of alanine aminotransferase Protect liver cells
and aspartate aminotransferase
7
8 BioMed Research International

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