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Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic Goto–Kakizaki rats
BACKGROUND/OBJECTIVE: Recently, intestinal electrical stimulation (IES) has been reported to result in weight loss; however, it is unclear whether it has a therapeutic potential for diabetes. The aim of the present study was to explore the potential hypoglycemic effects of IES and its possible mecha...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365494/ https://www.ncbi.nlm.nih.gov/pubmed/30728346 http://dx.doi.org/10.1038/s41387-019-0072-2 |
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author | Ouyang, Xiaojun Li, Shiying Tan, Yan Lin, Lin Yin, Jieyun Chen, Jiande D. Z. |
author_facet | Ouyang, Xiaojun Li, Shiying Tan, Yan Lin, Lin Yin, Jieyun Chen, Jiande D. Z. |
author_sort | Ouyang, Xiaojun |
collection | PubMed |
description | BACKGROUND/OBJECTIVE: Recently, intestinal electrical stimulation (IES) has been reported to result in weight loss; however, it is unclear whether it has a therapeutic potential for diabetes. The aim of the present study was to explore the potential hypoglycemic effects of IES and its possible mechanisms involving β cells in diabetic rats. SUBJECTS/METHODS: Diabetic Goto–Kakizaki (GK) rats were chronically implanted with one pair of electrodes in the duodenum. The oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed with or without IES, and plasma glucagon-like peptide-1 (GLP-1) and insulin level were measured. In the other two OGTT sessions, rats were treated with either Exendin (9–39) (GLP-1 antagonist) or Exendin (9–39) plus IES to investigate the underlying mechanism involving GLP-1. Gastric emptying and small intestinal transit were also measured with or without IES. In a chronic study, GK rats were treated with IES or Sham-IES for 8 weeks. Blood glucose, plasma GLP-1 and insulin level, body weight, and food intake were measured. Pancreas weight, islet β-cell apoptosis, and proliferation were also analyzed. RESULTS: Acute IES reduced blood glucose level from 60 to 120 min during OGTT by 16–20% (all p < 0.05, vs. Sham-IES). GLP-1 antagonist significantly blocked the inhibitory effect of IES on hyperglycemia from 15 to 120 min (all p < 0.05). IES accelerated the small intestinal transit by 15% (p = 0.004). After 8 weeks of chronic stimulation, IES significantly reduced blood glucose (p < 0.05) and body weight (p = 0.02) and increased the plasma GLP-1 concentration (p < 0.05). Furthermore, we observed that chronic IES reduced pancreatic β-cell apoptosis (p = 0.045), but showed no effects on β-cell proliferation. CONCLUSIONS: Our study firstly proved the hypoglycemic effect of IES in a rodent model of type 2 diabetes, possibly attributed to the increasing GLP-1 secretion and improvement in β-cell functions. |
format | Online Article Text |
id | pubmed-6365494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63654942019-02-15 Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic Goto–Kakizaki rats Ouyang, Xiaojun Li, Shiying Tan, Yan Lin, Lin Yin, Jieyun Chen, Jiande D. Z. Nutr Diabetes Article BACKGROUND/OBJECTIVE: Recently, intestinal electrical stimulation (IES) has been reported to result in weight loss; however, it is unclear whether it has a therapeutic potential for diabetes. The aim of the present study was to explore the potential hypoglycemic effects of IES and its possible mechanisms involving β cells in diabetic rats. SUBJECTS/METHODS: Diabetic Goto–Kakizaki (GK) rats were chronically implanted with one pair of electrodes in the duodenum. The oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed with or without IES, and plasma glucagon-like peptide-1 (GLP-1) and insulin level were measured. In the other two OGTT sessions, rats were treated with either Exendin (9–39) (GLP-1 antagonist) or Exendin (9–39) plus IES to investigate the underlying mechanism involving GLP-1. Gastric emptying and small intestinal transit were also measured with or without IES. In a chronic study, GK rats were treated with IES or Sham-IES for 8 weeks. Blood glucose, plasma GLP-1 and insulin level, body weight, and food intake were measured. Pancreas weight, islet β-cell apoptosis, and proliferation were also analyzed. RESULTS: Acute IES reduced blood glucose level from 60 to 120 min during OGTT by 16–20% (all p < 0.05, vs. Sham-IES). GLP-1 antagonist significantly blocked the inhibitory effect of IES on hyperglycemia from 15 to 120 min (all p < 0.05). IES accelerated the small intestinal transit by 15% (p = 0.004). After 8 weeks of chronic stimulation, IES significantly reduced blood glucose (p < 0.05) and body weight (p = 0.02) and increased the plasma GLP-1 concentration (p < 0.05). Furthermore, we observed that chronic IES reduced pancreatic β-cell apoptosis (p = 0.045), but showed no effects on β-cell proliferation. CONCLUSIONS: Our study firstly proved the hypoglycemic effect of IES in a rodent model of type 2 diabetes, possibly attributed to the increasing GLP-1 secretion and improvement in β-cell functions. Nature Publishing Group UK 2019-02-06 /pmc/articles/PMC6365494/ /pubmed/30728346 http://dx.doi.org/10.1038/s41387-019-0072-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ouyang, Xiaojun Li, Shiying Tan, Yan Lin, Lin Yin, Jieyun Chen, Jiande D. Z. Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic Goto–Kakizaki rats |
title | Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic Goto–Kakizaki rats |
title_full | Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic Goto–Kakizaki rats |
title_fullStr | Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic Goto–Kakizaki rats |
title_full_unstemmed | Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic Goto–Kakizaki rats |
title_short | Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic Goto–Kakizaki rats |
title_sort | intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic goto–kakizaki rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365494/ https://www.ncbi.nlm.nih.gov/pubmed/30728346 http://dx.doi.org/10.1038/s41387-019-0072-2 |
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