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Intestinal Electrical Stimulation Enhances Release of Postprandial Incretin Hormones Via Cholinergic Mechanisms

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Abstract

Introduction

Intestinal electrical stimulation (IES) has been reported to reduce body weight and improve glucose tolerance in obese and diabetic rats. Our study aimed to investigate possible IES mechanisms involving incretin hormones using intraduodenal glucose infusion in rats. We hypothesized that the enhanced release of postprandial glucagon-like peptide-1 (GLP-1) at early phase by IES was mediated through neuro/paracrine mechanisms involving the vagal nerve and glucose-dependent insulinotropic peptide (GIP).

Methods

Fifteen normal male Sprague-Dawley rats chronically implanted with duodenal electrodes for IES, and an intra-duodenum catheter for the infusion of glucose were studied in a series of sessions with IES of different parameters with and without atropine and M3 receptor antagonist. Blood samples were collected via the tail vein for the measurement of blood glucose, and plasma GLP-1, and GIP.

Results

(1) Compared to sham-IES, IES of 0.3 ms reduced blood glucose by 16.5–28.4% between 30 and 120 min (all time points p < 0.05), and IES of 3-ms reduced blood glucose at 60 (12.6%) and 90 min (11.8%). IES of 0.3 ms showed a greater hypoglycemic effect than 3 ms (p = 0.024) at 30 min. (2) IES elevated plasma GLP-1 with 0.3 ms (p = 0.001) and with 3 ms p = 0.03). (3) IES substantially elevated plasma GIP with 0.3 ms (p = 0.002) and with 3 ms (p < 0.001). (4) Pretreatment of atropine and the M3 receptor antagonist 4-DAMP blocked the effects of IES on GLP-1, GIP, and blood glucose.

Conclusions

IES reduces postprandial blood glucose by enhancing the release of GLP-1 and GIP mediated via the cholinergic mechanism.

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Funding

This study is supported by a grant from NIH: R01DK107754.

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Author notes

  1. Yan Dong and Yiling Zhang contributed equally to this work.

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, 21224, USA

    Yan Dong, Yiling Zhang, Shiying Li & Jiande D. Z. Chen

  2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA

    Shiying Li & Jiande D. Z. Chen

Authors
  1. Yan Dong
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  2. Yiling Zhang
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  3. Shiying Li
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  4. Jiande D. Z. Chen
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Correspondence to Jiande D. Z. Chen.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institutional and/or national research committee. This article does not contain any studies with human performed by any of the authors.

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Dong, Y., Zhang, Y., Li, S. et al. Intestinal Electrical Stimulation Enhances Release of Postprandial Incretin Hormones Via Cholinergic Mechanisms. OBES SURG 31, 1957–1966 (2021). https://doi.org/10.1007/s11695-021-05228-w

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