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NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells
Type 2 diabetes mellitus (T2DM) remains one of the most pressing health issues facing modern society. Several antidiabetic drugs are currently in clinical use to treat hyperglycaemia, but there is a need for new treatments that effectively restore pancreatic islet function in patients. Recent studie...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091448/ https://www.ncbi.nlm.nih.gov/pubmed/35571112 http://dx.doi.org/10.3389/fphar.2022.861311 |
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author | Cyranka, Malgorzata Monfeuga, Thomas Vedovato, Natascia Larabee, Chelsea M Chandran, Anandhakumar Toledo, Enrique M de Wet, Heidi |
author_facet | Cyranka, Malgorzata Monfeuga, Thomas Vedovato, Natascia Larabee, Chelsea M Chandran, Anandhakumar Toledo, Enrique M de Wet, Heidi |
author_sort | Cyranka, Malgorzata |
collection | PubMed |
description | Type 2 diabetes mellitus (T2DM) remains one of the most pressing health issues facing modern society. Several antidiabetic drugs are currently in clinical use to treat hyperglycaemia, but there is a need for new treatments that effectively restore pancreatic islet function in patients. Recent studies reported that both murine and human pancreatic islets exhibit enhanced insulin release and β-cell viability in response to N-methyl-D-aspartate (NMDA) receptor antagonists. Furthermore, oral administration of dextromethorphan, an over-the-counter NMDA receptor antagonist, to diabetic patients in a small clinical trial showed improved glucose tolerance and increased insulin release. However, the effects of NMDA receptor antagonists on the secretion of the incretin hormone GLP-1 was not tested, and nothing is known regarding how NMDA receptor antagonists may alter the secretion of gut hormones. This study demonstrates for the first time that, similar to β-cells, the NMDA receptor antagonist MK-801 increases the release of GLP-1 from a murine L-cell enteroendocrine model cell line, GLUTag cells. Furthermore, we report the 3′ mRNA expression profiling of GLUTag cells, with a specific focus on glutamate-activated receptors. We conclude that if NMDA receptor antagonists are to be pursued as an alternative, orally administered treatment for T2DM, it is essential that the effects of these drugs on the release of gut hormones, and specifically the incretin hormones, are fully investigated. |
format | Online Article Text |
id | pubmed-9091448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90914482022-05-12 NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells Cyranka, Malgorzata Monfeuga, Thomas Vedovato, Natascia Larabee, Chelsea M Chandran, Anandhakumar Toledo, Enrique M de Wet, Heidi Front Pharmacol Pharmacology Type 2 diabetes mellitus (T2DM) remains one of the most pressing health issues facing modern society. Several antidiabetic drugs are currently in clinical use to treat hyperglycaemia, but there is a need for new treatments that effectively restore pancreatic islet function in patients. Recent studies reported that both murine and human pancreatic islets exhibit enhanced insulin release and β-cell viability in response to N-methyl-D-aspartate (NMDA) receptor antagonists. Furthermore, oral administration of dextromethorphan, an over-the-counter NMDA receptor antagonist, to diabetic patients in a small clinical trial showed improved glucose tolerance and increased insulin release. However, the effects of NMDA receptor antagonists on the secretion of the incretin hormone GLP-1 was not tested, and nothing is known regarding how NMDA receptor antagonists may alter the secretion of gut hormones. This study demonstrates for the first time that, similar to β-cells, the NMDA receptor antagonist MK-801 increases the release of GLP-1 from a murine L-cell enteroendocrine model cell line, GLUTag cells. Furthermore, we report the 3′ mRNA expression profiling of GLUTag cells, with a specific focus on glutamate-activated receptors. We conclude that if NMDA receptor antagonists are to be pursued as an alternative, orally administered treatment for T2DM, it is essential that the effects of these drugs on the release of gut hormones, and specifically the incretin hormones, are fully investigated. Frontiers Media S.A. 2022-04-27 /pmc/articles/PMC9091448/ /pubmed/35571112 http://dx.doi.org/10.3389/fphar.2022.861311 Text en Copyright © 2022 Cyranka, Monfeuga, Vedovato, Larabee, Chandran, Toledo and de Wet. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Cyranka, Malgorzata Monfeuga, Thomas Vedovato, Natascia Larabee, Chelsea M Chandran, Anandhakumar Toledo, Enrique M de Wet, Heidi NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells |
title | NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells |
title_full | NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells |
title_fullStr | NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells |
title_full_unstemmed | NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells |
title_short | NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells |
title_sort | nmda receptor antagonists increase the release of glp-1 from gut endocrine cells |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091448/ https://www.ncbi.nlm.nih.gov/pubmed/35571112 http://dx.doi.org/10.3389/fphar.2022.861311 |
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