Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity

Impaired glucose homeostasis and energy balance are integral to the pathophysiology of diabetes and obesity. Here we show that administration of a glycine transporter 1 (GlyT1) inhibitor, or molecular GlyT1 knockdown, in the dorsal vagal complex (DVC) suppresses glucose production, increases glucose...

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Main Authors:	Yue, Jessica T. Y., Abraham, Mona A., Bauer, Paige V., LaPierre, Mary P., Wang, Peili, Duca, Frank A., Filippi, Beatrice M., Chan, Owen, Lam, Tony K. T.
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121412/

id	pubmed-5121412
recordtype	oai_dc
spelling	pubmed-51214122016-12-02 Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity Yue, Jessica T. Y. Abraham, Mona A. Bauer, Paige V. LaPierre, Mary P. Wang, Peili Duca, Frank A. Filippi, Beatrice M. Chan, Owen Lam, Tony K. T. Article Impaired glucose homeostasis and energy balance are integral to the pathophysiology of diabetes and obesity. Here we show that administration of a glycine transporter 1 (GlyT1) inhibitor, or molecular GlyT1 knockdown, in the dorsal vagal complex (DVC) suppresses glucose production, increases glucose tolerance and reduces food intake and body weight gain in healthy, obese and diabetic rats. These findings provide proof of concept that GlyT1 inhibition in the brain improves glucose and energy homeostasis. Considering the clinical safety and efficacy of GlyT1 inhibitors in raising glycine levels in clinical trials for schizophrenia, we propose that GlyT1 inhibitors have the potential to be repurposed as a treatment of both obesity and diabetes. Nature Publishing Group 2016-11-22 /pmc/articles/PMC5121412/ /pubmed/27874011 http://dx.doi.org/10.1038/ncomms13501 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yue, Jessica T. Y. Abraham, Mona A. Bauer, Paige V. LaPierre, Mary P. Wang, Peili Duca, Frank A. Filippi, Beatrice M. Chan, Owen Lam, Tony K. T.
spellingShingle	Yue, Jessica T. Y. Abraham, Mona A. Bauer, Paige V. LaPierre, Mary P. Wang, Peili Duca, Frank A. Filippi, Beatrice M. Chan, Owen Lam, Tony K. T. Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity
author_facet	Yue, Jessica T. Y. Abraham, Mona A. Bauer, Paige V. LaPierre, Mary P. Wang, Peili Duca, Frank A. Filippi, Beatrice M. Chan, Owen Lam, Tony K. T.
author_sort	Yue, Jessica T. Y.
title	Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity
title_short	Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity
title_full	Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity
title_fullStr	Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity
title_full_unstemmed	Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity
title_sort	inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity
description	Impaired glucose homeostasis and energy balance are integral to the pathophysiology of diabetes and obesity. Here we show that administration of a glycine transporter 1 (GlyT1) inhibitor, or molecular GlyT1 knockdown, in the dorsal vagal complex (DVC) suppresses glucose production, increases glucose tolerance and reduces food intake and body weight gain in healthy, obese and diabetic rats. These findings provide proof of concept that GlyT1 inhibition in the brain improves glucose and energy homeostasis. Considering the clinical safety and efficacy of GlyT1 inhibitors in raising glycine levels in clinical trials for schizophrenia, we propose that GlyT1 inhibitors have the potential to be repurposed as a treatment of both obesity and diabetes.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121412/
_version_	1613739236850139136

Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity

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