Enhanced insulin sensitivity and acute regulation of metabolic genes and signaling pathways after a single electrical or manual acupuncture session in female insulin-resistant rats

Benrick, Anna; Maliqueo, Manuel; Johansson, Julia; Sun, Miao; Wu, Xiaoke; Mannerås-Holm, Louise; Stener-Victorin, Elisabet

doi:10.1007/s00592-014-0645-4

Cited by 30 publications

(28 citation statements)

References 33 publications

(54 reference statements)

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“…In the present study, we decided to give acupuncture 3 times/week because lower treatment frequency (1–2 times/week) did not improve insulin sensitivity in women with PCOS . Comparisons between manual stimulation and electrical stimulation of the needles demonstrate that electroacupuncture improves insulin sensitivity and modulates skeletal muscle gene and protein expression more than manual stimulation of the needles in rats . In the present study, we combined electrical stimulation with manual stimulation of needles which is a common stimulation paradigm in the clinic.…”

Section: Introductionmentioning

confidence: 95%

Changes in HbA_1c and circulating and adipose tissue androgen levels in overweight‐obese women with polycystic ovary syndrome in response to electroacupuncture

Stener‐Victorin

Maliqueo

Soligo

et al. 2016

Obesity Science & Practice

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SummaryAimInsulin sensitivity is ~40% lower in women with polycystic ovary syndrome (PCOS) than in controls. We tested the hypothesis that 5 weeks of electroacupuncture treatment improves glucose regulation and androgen levels in overweight/obese women with PCOS.Material and MethodsSeventeen women with PCOS, aged 18 to 38 years, with a body mass index (BMI) ≥25 kg/m2 and diagnosed with PCOS were included in this experimental and feasibility study and subjected to five weeks of electroacupuncture treatments three times/week. The primary outcome was changes in whole‐body glucose homeostasis measured by euglycemic hyperinsulinemic clamp before and after the intervention. Secondary outcome were changes in HbA1c, circulating catecholamines, adipocyte size and adipose tissue expression of sex steroids and nerve growth factor (NGF).ResultsNo significant change in glucose homeostasis was observed, but HbA1c decreased by 9.5% (p = 0.004), circulating testosterone decreased by 22% (p = 0.0007) and dihydrotestosterone decreased by 12% (p = 0.007). The two vagal activity markers of plasma serotonin levels and the dopamine metabolite homovanillic acid decreased by 21% (p = 0.027) and 20% (p = 0.011), respectively. Adipose tissue concentrations of testosterone decreased by 18% (p = 0.049), and androstenedione decreased by 13% (p = 0.035), and mature NGF/proNGF ratio, a marker of sympathetic activity, increased (p = 0.04). These changes occurred without changes in anthropometrics.ConclusionFive weeks of electroacupuncture treatment improves HbA1c and circulating and adipose tissue androgens in women with PCOS. This effect is mediated, at least in part, via modulation of vagal activity and adipose tissue sympathetic activity. Based on these findings, we have recently initiated a randomized controlled study (NTC02647827).

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Section: Introductionmentioning

confidence: 95%

Changes in HbA_1c and circulating and adipose tissue androgen levels in overweight‐obese women with polycystic ovary syndrome in response to electroacupuncture

Stener‐Victorin

Maliqueo

Soligo

et al. 2016

Obesity Science & Practice

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“…We previously demonstrated that a single bout of EA in rats is superior to manual stimulation of the needles, but they are equally effective during the poststimulation period, indicating that it is the activation of sensory afferents rather than muscle contractions per se that causes the observed changes (15). Here, we show that the increased glucose uptake in rats is mediated by activation of sympathetic nerves because blocking adrenergic receptors reverses the increased glucose uptake.…”

Section: Discussionmentioning

confidence: 99%

“…The clamp was performed in animals under anesthesia (15). Insulin (Actrapid, Novo Nordisk, Denmark) was continuously infused at 8 mU/kg/min, and glucose was infused to maintain a blood glucose level of 6 mM.…”

Section: Euglycemic-hyperinsulinemic Clampmentioning

confidence: 99%

“…A single bout of low‐frequency EA increases whole‐body glucose uptake during and after stimulation in both controls and insulin‐resistant rats (15). However, there is only limited evidence in support of the effectiveness of EA for improving glucose homeostasis or insulin sensitivity during and after stimulation in humans (16), and there is no study evaluating the effect in insulin‐resistant subjects.…”

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confidence: 99%

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Autonomic nervous system activation mediates the increase in whole‐body glucose uptake in response to electroacupuncture

Benrick

Kokosar

et al. 2017

FASEB j.

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A single bout of low-frequency electroacupuncture (EA) causing muscle contractions increases whole-body glucose uptake in insulin-resistant rats. We explored the underlying mechanism of this finding and whether it can be translated into clinical settings. Changes in glucose infusion rate (GIR) were measured by euglycemic-hyperinsulinemic clamp during and after 45 min of low-frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS) and 21 controls matched for age, weight, and body mass index (experiment 1) and in rats receiving autonomic receptor blockers (experiment 2). GIR was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS, but not in controls, suggesting increased sympathetic-driven adipose tissue metabolism. Administration of α-/β-adrenergic receptor blockers in rats blocked the increase in GIR in response to EA. Muscarinic and dopamine receptor antagonist also blocked the response but with slower onset. In conclusion, a single bout of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.-Benrick, A., Kokosar, M., Hu, M., Larsson, M., Maliqueo, M., Marcondes, R. R., Soligo, M., Protto, V., Jerlhag, E., Sazonova, A., Behre, C. J., Højlund, K., Thorén, P., Stener-Victorin, E. Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture.

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“…Other findings suggest that electrical acupuncture stimulation affects more functional signaling pathways related to insulin sensitivity, while manual stimulation of acupuncture needles has a greater effect on glucose tolerance [23]. Furthermore, in female insulin-resistant rats both electrical and manual acupuncture stimulation enhances insulin sensitivity via activation of sensory afferents [24]. Our prospective pilot study (ClinicalTrials.gov NCT02026323) [25] of acupuncture affecting the insulin sensitivity in 81 cases of women with PCOS with IR showed that acupuncture has a significant effect on improving the insulin sensitivity in these patients.…”

Section: Introductionmentioning

confidence: 99%

Acupuncture treatment for insulin sensitivity of women with polycystic ovary syndrome and insulin resistance: a study protocol for a randomized controlled trial

Stener-Victorin

et al. 2017

Trials

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BackgroundOur prospective pilot study of acupuncture affecting insulin sensitivity on polycystic ovary syndrome (PCOS) combined with insulin resistance (IR) showed that acupuncture had a significant effect on improving the insulin sensitivity of PCOS. But there is still no randomized controlled trial to determine the effect of acupuncture on the insulin sensitivity in women with PCOS and IR. In this article, we present the protocol of a randomized controlled trial to compare the effect of true acupuncture on the insulin sensitivity of these patients compared with metformin and sham acupuncture. Acupuncture may be an effective therapeutic alternative that is superior to metformin and sham acupuncture in improving the insulin sensitivity of PCOS combined with IR.MethodsThis study is a multi-center, controlled, double-blind, and randomized clinical trial aiming to evaluate the effect of acupuncture on the insulin sensitivity in PCOS combined with IR. In total 342 patients diagnosed with PCOS and IR will be enrolled. Participants will be randomized to one of the three groups: (1) true acupuncture + metformin placebo; (2) sham acupuncture + metformin, and (3) sham acupuncture + metformin placebo. Participants and assessors will be blinded. The acupuncture intervention will be given 3 days per week for a total of 48 treatment sessions during 4 months. Metformin (0.5 g per pill) or placebo will be given, three times per day, and for 4 months.Primary outcome measures are changes in homeostasis model assessment of insulin resistance (HOMA-IR) and improvement rate of HOMA-IR by oral glucose tolerance test (OGTT) and insulin releasing test (Ins). Secondary outcome measures are homeostasis model assessment-β (HOMA-β), area under the curve for glucose and insulin, frequency of regular menstrual cycles and ovulation, body composition, metabolic profile, hormonal profile, questionnaires, side effect profile, and expectation and credibility of treatment.Outcome measures are collected at baseline, at the end of treatments, and 3 months after the last acupuncture treatment. On completion of the screening visit, randomization will be conducted using a central randomization system.DiscussionThis study will investigate the effects of acupuncture on the insulin sensitivity of PCOS and IR women compared with metformin and sham acupuncture. We will test whether true acupuncture with needles placed in skeletal muscles and stimulated manually and by electrical stimulation is more effective than metformin and sham acupuncture with superficial needle placement with no manual or electrical stimulation in improving the insulin sensitivity in PCOS women with IR.Trial registrationClinicalTrials.gov, NCT02491333; Chinese Clinical Trial Registry, ChiCTR-ICR-15006639. Registered on 24 June 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1854-2) contains supplementary material, which is available to authorized users.

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Enhanced insulin sensitivity and acute regulation of metabolic genes and signaling pathways after a single electrical or manual acupuncture session in female insulin-resistant rats

Cited by 30 publications

References 33 publications

Changes in HbA_1c and circulating and adipose tissue androgen levels in overweight‐obese women with polycystic ovary syndrome in response to electroacupuncture

Changes in HbA_1c and circulating and adipose tissue androgen levels in overweight‐obese women with polycystic ovary syndrome in response to electroacupuncture

Autonomic nervous system activation mediates the increase in whole‐body glucose uptake in response to electroacupuncture

Acupuncture treatment for insulin sensitivity of women with polycystic ovary syndrome and insulin resistance: a study protocol for a randomized controlled trial

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Enhanced insulin sensitivity and acute regulation of metabolic genes and signaling pathways after a single electrical or manual acupuncture session in female insulin-resistant rats

Cited by 30 publications

References 33 publications

Changes in HbA1c and circulating and adipose tissue androgen levels in overweight‐obese women with polycystic ovary syndrome in response to electroacupuncture

Changes in HbA1c and circulating and adipose tissue androgen levels in overweight‐obese women with polycystic ovary syndrome in response to electroacupuncture

Autonomic nervous system activation mediates the increase in whole‐body glucose uptake in response to electroacupuncture

Acupuncture treatment for insulin sensitivity of women with polycystic ovary syndrome and insulin resistance: a study protocol for a randomized controlled trial

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Changes in HbA_1c and circulating and adipose tissue androgen levels in overweight‐obese women with polycystic ovary syndrome in response to electroacupuncture

Changes in HbA_1c and circulating and adipose tissue androgen levels in overweight‐obese women with polycystic ovary syndrome in response to electroacupuncture