Intracellular signalling pathways associated with the glucose-lowering effect of ST36 electroacupuncture in streptozotocin-induced diabetic rats

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Abstract

Background and aim

Previous animal studies have reported a glucose-lowering effect of electroacupuncture (EA) and suggested that the mechanisms are closely related to intracellular signalling pathways. The aim of this study was to screen for potential intracellular signalling pathways that are upregulated by EA at ST36 bilaterally in rats with diabetes mellitus (DM) using microarray analysis.

Methods

Streptozotocin (STZ)-induced diabetic rats were randomly assigned to experimental (EA, n=8) or control (non-EA, n=8) groups. Plasma glucose levels were measured at baseline and after 30 and 60 min, and microarray analysis was performed on samples of gastrocnemius muscle.

Results

Relative to baseline values, EA significantly reduced plasma levels of glucose at 30 and 60 min. The microarray pathway analysis showed that cell adhesion molecules and type 1 DM gene sets were both upregulated in EA versus non-EA groups (p<0.05).

Conclusions

Cell adhesion molecules might be related to the glucose-lowering effect induced by EA in rats with STZ-induced type 1 diabetes. Further research will be required to examine the involvement of related intracellular signalling pathways.

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Activation of Wnt/β-Catenin Signaling Increases Insulin Sensitivity through a Reciprocal Regulation of Wnt10b and SREBP-1c in Skeletal Muscle Cells

Mounira Abiola, Maryline Favier, Eleni Christodoulou-Vafeiadou … (2009)

Background Intramyocellular lipid accumulation is strongly related to insulin resistance in humans, and we have shown that high glucose concentration induced de novo lipogenesis and insulin resistance in murin muscle cells. Alterations in Wnt signaling impact the balance between myogenic and adipogenic programs in myoblasts, partly due to the decrease of Wnt10b protein. As recent studies point towards a role for Wnt signaling in the pathogenesis of type 2 diabetes, we hypothesized that activation of Wnt signaling could play a crucial role in muscle insulin sensitivity. Methodology/Principal Findings Here we demonstrate that SREBP-1c and Wnt10b display inverse expression patterns during muscle ontogenesis and regeneration, as well as during satellite cells differentiation. The Wnt/β-catenin pathway was reactivated in contracting myotubes using siRNA mediated SREBP-1 knockdown, Wnt10b over-expression or inhibition of GSK-3β, whereas Wnt signaling was inhibited in myoblasts through silencing of Wnt10b. SREBP-1 knockdown was sufficient to induce Wnt10b protein expression in contracting myotubes and to activate the Wnt/β-catenin pathway. Conversely, silencing Wnt10b in myoblasts induced SREBP-1c protein expression, suggesting a reciprocal regulation. Stimulation of the Wnt/β-catenin pathway i) drastically decreased SREBP-1c protein and intramyocellular lipid deposition in myotubes; ii) increased basal glucose transport in both insulin-sensitive and insulin-resistant myotubes through a differential activation of Akt and AMPK pathways; iii) restored insulin sensitivity in insulin-resistant myotubes. Conclusions/Significance We conclude that activation of Wnt/β-catenin signaling in skeletal muscle cells improved insulin sensitivity by i) decreasing intramyocellular lipid deposition through downregulation of SREBP-1c; ii) increasing insulin effects through a differential activation of the Akt/PKB and AMPK pathways; iii) inhibiting the MAPK pathway. A crosstalk between these pathways and Wnt/β-catenin signaling in skeletal muscle opens the exciting possibility that organ-selective modulation of Wnt signaling might become an attractive therapeutic target in regenerative medicine and to treat obese and diabetic populations.

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Recent advances in our understanding of insulin action and insulin resistance.

Nhu D. Le, Y Zick (2001)

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An insulin-dependent hypoglycaemia induced by electroacupuncture at the Zhongwan (CV12) acupoint in diabetic rats.

June J. Cheng, I-Ju Liu, Martin Chang … (1999)

Acupuncture at the Zhongwan acupoint has been widely used in traditional Chinese medicine to relieve symptoms of diabetes mellitus. Our study investigated the effect on plasma glucose of electroacupuncture applied at the Zhongwan acupoint in rat diabetic models. Plasma concentrations of insulin, glucagon and beta-endorphin- were also determined using radioimmunoassay. A decrease in plasma glucose was observed in rats after electroacupuncture (15 Hz, 10 mA) for 30 min at the Zhongwan acupoint. This was observed in normal rats and rat models with Type II (non-insulin-dependent) diabetes mellitus. No significant effect on plasma glucose was observed in rat models with Type I (insulin-dependent) diabetes mellitus: neither the streptozotocin (STZ)-induced diabetic rats nor the genetic (BB/W) rats. Further, the hypoglycaemic action of electroacupuncture stimulation disappeared in rats with insulin-resistance induced by an injection of human long-acting insulin repeated daily to cause the loss of tolbutamide-induced hypoglycaemia. An insulin-related action can thus be hypothesised. This hypothesis is supported by an increase in plasma insulin-like immunoreactivity after electroacupuncture stimulation in normal rats. Participation of glucagon was ruled out because there was no change in plasma glucagon-like immunoreactivity resulting from electroacupuncture stimulation. In addition to an increase in plasma beta-endorphin-like immunoreactivity, the plasma glucose lowering action of electroacupuncture stimulation at Zhongwan acupoint was abolished by naloxone in a sufficient dose to block opioid receptors. Thus we suggest that electroacupuncture stimulation at the Zhongwan acupoint induces secretion of endogenous beta-endorphin which reduces plasma glucose concentration in an insulin-dependent manner.

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Author and article information

Journal

Journal ID (nlm-ta): Acupunct Med

Journal ID (iso-abbrev): Acupunct Med

Journal ID (hwp): acupmed

Journal ID (publisher-id): aim

Title: Acupuncture in Medicine

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Print): 0964-5284

ISSN (Electronic): 1759-9873

Publication date (Print): October 2015

Publication date (Electronic): 29 May 2015

Volume: 33

Issue: 5

Pages: 395-399

Affiliations

[1 ]Department of Orthopedics, Taichung Veterans General Hospital , Taichung City, Taiwan

[2 ]Institute of Molecular Medicine, College of Life Science, National Tsing Hua University , Hsinchu City, Taiwan

[3 ]Department of Nursing, Hung Kuang University , Taiwan

[4 ]Department of Acupuncture, China Medical University Hospital , Taichung City, Taiwan

[5 ]School of Chinese Medicine, China Medical University , Taichung City, Taiwan

[6 ]Department of Medicinal Botanicals and Health Applications, Da-Yeh University , Changhua County, Taiwan

Author notes

[Correspondence to ] Professor Kuan-Rong Lee and Professor Shih-Liang Chang, Department of Medicinal Botanicals and Health Applications, Da-Yeh University, No. 168, university Road, Dacun, Changhua County, Taiwan; slchang@mail.dyu.edu.tw or slc0124@gmail.com

Article

Publisher ID: acupmed-2014-010718

DOI: 10.1136/acupmed-2014-010718

PMC ID: 4680132

PubMed ID: 26025382

SO-VID: 47c117fc-5d8e-47f5-b724-14714b64681d

License:

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

History

Date accepted : 11 May 2015

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ScienceOpen disciplines: Complementary & Alternative medicine

Keywords: diabetes

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ScienceOpen disciplines: Complementary & Alternative medicine

Keywords: diabetes

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Intracellular signalling pathways associated with the glucose-lowering effect of ST36 electroacupuncture in streptozotocin-induced diabetic rats

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Abstract

Background and aim

Methods

Results

Conclusions

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The International Journal of Person Centered Medicine

Most cited references 22

Activation of Wnt/β-Catenin Signaling Increases Insulin Sensitivity through a Reciprocal Regulation of Wnt10b and SREBP-1c in Skeletal Muscle Cells

Recent advances in our understanding of insulin action and insulin resistance.

An insulin-dependent hypoglycaemia induced by electroacupuncture at the Zhongwan (CV12) acupoint in diabetic rats.

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Cited by 4

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