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Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats
BACKGROUND: Our recent findings support the idea that 3-deoxyglucosone (3DG), a dietary composition, has been suggested as an independent factor for the development of prediabetes. Secretion of glucagon-like peptide-1 (GLP-1) has been suggested to be impaired in T2DM and in conditions associated wit...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129672/ https://www.ncbi.nlm.nih.gov/pubmed/27956941 http://dx.doi.org/10.1186/s13098-016-0194-9 |
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author | Zhang, Lurong Song, Xiudao Zhou, Liang Liang, Guoqiang Xu, Heng Wang, Fei Huang, Fei Jiang, Guorong |
author_facet | Zhang, Lurong Song, Xiudao Zhou, Liang Liang, Guoqiang Xu, Heng Wang, Fei Huang, Fei Jiang, Guorong |
author_sort | Zhang, Lurong |
collection | PubMed |
description | BACKGROUND: Our recent findings support the idea that 3-deoxyglucosone (3DG), a dietary composition, has been suggested as an independent factor for the development of prediabetes. Secretion of glucagon-like peptide-1 (GLP-1) has been suggested to be impaired in T2DM and in conditions associated with hyperglycemia. Since low oral bioavailability of 3DG has been indicated in a single administration study, in the present study we examined if 3DG is capable of accumulating in intestinal tissue of rats after 2-week administration of 3DG, and the 3DG treatment affects GLP-1 secretion and glucose tolerance. METHODS: Rats were administered by gastric gavage for 2 weeks. We measured 3DG contents of intestinal tissues (by HPLC), plasma levels of total GLP-1 (by ELISA), insulin and glucagon (both by radioimmunoassay) and blood glucose concentrations. The expressions of the sweet receptor subunits (TAS1R2, TAS1R3) and its downstream molecule TRPM5 in duodenum and colon tissues of rats were quantified by WB. We examined GLP-1 secretion in enteroendocrine STC-1 cells exposured to 3DG. RESULTS: 3DG treatment for 2 weeks increased 3DG content of intestinal tissues, fasting blood glucose concentration, and reduced plasma concentrations of GLP-1 and insulin at fasting and 15 and 180 min after the glucose load and oral glucose tolerance in conjunction with increased plasma glucagon concentrations. The expressions of TAS1R2, TAS1R3 and TRPM5 were shown to be reduced whereas 3DG treatment did not affect plasma dipeptidyl peptidase-4 activity, indicating an impaired GLP-1 secretion in 3DG-treated rats. This idea was further supported by the fact that exposure to 3DG directly decrease GLP-1 secretion in STC-1. CONCLUSION: It is the first demonstration that 3DG was capable of accumulating in intestinal tissue and thereby decreased secretion of GLP-1 and insulin in a similar manner. 3DG-treated rats developed impaired glucose regulation (IGR) with obviously pancreatic islet cell dysfunction. It is further concluded that a decrease in the biological function of GLP-1 resulting from the decreased GLP-1 secretion is the most likely mechanism for the impaired insulin secretion, which ultimately promoted the development of IGR. These results will also contribute to a better understanding of the significance for restoring physiological GLP-1 secretion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13098-016-0194-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5129672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-51296722016-12-12 Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats Zhang, Lurong Song, Xiudao Zhou, Liang Liang, Guoqiang Xu, Heng Wang, Fei Huang, Fei Jiang, Guorong Diabetol Metab Syndr Research BACKGROUND: Our recent findings support the idea that 3-deoxyglucosone (3DG), a dietary composition, has been suggested as an independent factor for the development of prediabetes. Secretion of glucagon-like peptide-1 (GLP-1) has been suggested to be impaired in T2DM and in conditions associated with hyperglycemia. Since low oral bioavailability of 3DG has been indicated in a single administration study, in the present study we examined if 3DG is capable of accumulating in intestinal tissue of rats after 2-week administration of 3DG, and the 3DG treatment affects GLP-1 secretion and glucose tolerance. METHODS: Rats were administered by gastric gavage for 2 weeks. We measured 3DG contents of intestinal tissues (by HPLC), plasma levels of total GLP-1 (by ELISA), insulin and glucagon (both by radioimmunoassay) and blood glucose concentrations. The expressions of the sweet receptor subunits (TAS1R2, TAS1R3) and its downstream molecule TRPM5 in duodenum and colon tissues of rats were quantified by WB. We examined GLP-1 secretion in enteroendocrine STC-1 cells exposured to 3DG. RESULTS: 3DG treatment for 2 weeks increased 3DG content of intestinal tissues, fasting blood glucose concentration, and reduced plasma concentrations of GLP-1 and insulin at fasting and 15 and 180 min after the glucose load and oral glucose tolerance in conjunction with increased plasma glucagon concentrations. The expressions of TAS1R2, TAS1R3 and TRPM5 were shown to be reduced whereas 3DG treatment did not affect plasma dipeptidyl peptidase-4 activity, indicating an impaired GLP-1 secretion in 3DG-treated rats. This idea was further supported by the fact that exposure to 3DG directly decrease GLP-1 secretion in STC-1. CONCLUSION: It is the first demonstration that 3DG was capable of accumulating in intestinal tissue and thereby decreased secretion of GLP-1 and insulin in a similar manner. 3DG-treated rats developed impaired glucose regulation (IGR) with obviously pancreatic islet cell dysfunction. It is further concluded that a decrease in the biological function of GLP-1 resulting from the decreased GLP-1 secretion is the most likely mechanism for the impaired insulin secretion, which ultimately promoted the development of IGR. These results will also contribute to a better understanding of the significance for restoring physiological GLP-1 secretion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13098-016-0194-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-29 /pmc/articles/PMC5129672/ /pubmed/27956941 http://dx.doi.org/10.1186/s13098-016-0194-9 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zhang, Lurong Song, Xiudao Zhou, Liang Liang, Guoqiang Xu, Heng Wang, Fei Huang, Fei Jiang, Guorong Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats |
title | Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats |
title_full | Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats |
title_fullStr | Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats |
title_full_unstemmed | Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats |
title_short | Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats |
title_sort | accumulation of intestinal tissue 3-deoxyglucosone attenuated glp-1 secretion and its insulinotropic effect in rats |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129672/ https://www.ncbi.nlm.nih.gov/pubmed/27956941 http://dx.doi.org/10.1186/s13098-016-0194-9 |
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