Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Cyranka, Malgorzata, Monfeuga, Thomas, Vedovato, Natascia, Larabee, Chelsea M, Chandran, Anandhakumar, Toledo, Enrique M, de Wet, Heidi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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
_version_ 1784704925917249536
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
work_keys_str_mv AT cyrankamalgorzata nmdareceptorantagonistsincreasethereleaseofglp1fromgutendocrinecells
AT monfeugathomas nmdareceptorantagonistsincreasethereleaseofglp1fromgutendocrinecells
AT vedovatonatascia nmdareceptorantagonistsincreasethereleaseofglp1fromgutendocrinecells
AT larabeechelseam nmdareceptorantagonistsincreasethereleaseofglp1fromgutendocrinecells
AT chandrananandhakumar nmdareceptorantagonistsincreasethereleaseofglp1fromgutendocrinecells
AT toledoenriquem nmdareceptorantagonistsincreasethereleaseofglp1fromgutendocrinecells
AT dewetheidi nmdareceptorantagonistsincreasethereleaseofglp1fromgutendocrinecells