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Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics

Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of type 1 diabetes. Because little is known about its absorption and effects in humans, we investigated the pharmacokinetics and pharmacodynamics of GABA in healthy volunteers. Twelve subjects were subjected to an open-...

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Autores principales: Li, Junfeng, Zhang, Zhaoyun, Liu, Xiaoxia, Wang, Yi, Mao, Fei, Mao, Junjun, Lu, Xiaolan, Jiang, Dongdong, Wan, Yun, Lv, Jia-Ying, Cao, Guoying, Zhang, Jing, Zhao, Naiqing, Atkinson, Mark, Greiner, Dale L., Prud'homme, Gerald J., Jiao, Zheng, Li, Yiming, Wang, Qinghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639630/
https://www.ncbi.nlm.nih.gov/pubmed/26617516
http://dx.doi.org/10.3389/fphar.2015.00260
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author Li, Junfeng
Zhang, Zhaoyun
Liu, Xiaoxia
Wang, Yi
Mao, Fei
Mao, Junjun
Lu, Xiaolan
Jiang, Dongdong
Wan, Yun
Lv, Jia-Ying
Cao, Guoying
Zhang, Jing
Zhao, Naiqing
Atkinson, Mark
Greiner, Dale L.
Prud'homme, Gerald J.
Jiao, Zheng
Li, Yiming
Wang, Qinghua
author_facet Li, Junfeng
Zhang, Zhaoyun
Liu, Xiaoxia
Wang, Yi
Mao, Fei
Mao, Junjun
Lu, Xiaolan
Jiang, Dongdong
Wan, Yun
Lv, Jia-Ying
Cao, Guoying
Zhang, Jing
Zhao, Naiqing
Atkinson, Mark
Greiner, Dale L.
Prud'homme, Gerald J.
Jiao, Zheng
Li, Yiming
Wang, Qinghua
author_sort Li, Junfeng
collection PubMed
description Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of type 1 diabetes. Because little is known about its absorption and effects in humans, we investigated the pharmacokinetics and pharmacodynamics of GABA in healthy volunteers. Twelve subjects were subjected to an open-labeled, three-period trial involving sequential oral administration of placebo, 2 g GABA once, and 2 g GABA three times/day for 7 days, with a 7-day washout between each period. GABA was rapidly absorbed (Tmax: 0.5 ~ 1 h) with the half-life (t1/2) of 5 h. No accumulation was observed after repeated oral GABA administration for 7 days. Remarkably, GABA significantly increased circulating insulin levels in the subjects under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p < 0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p < 0.01). GABA also increased glucagon levels only under fasting conditions (1.3-fold, single dose, p < 0.05; 1.5-fold, repeated dose, p < 0.01). However, there were no significant differences in the insulin-to-glucagon ratio and no significant change in glucose levels in these healthy subjects during the study period. Importantly, GABA significantly decreased glycated albumin levels in the repeated dosing period. Subjects with repeated dosing showed an elevated incidence of minor adverse events in comparison to placebo or the single dosing period, most notably transient discomforts such as dizziness and sore throat. However, there were no serious adverse events observed throughout the study. Our data show that GABA is rapidly absorbed and tolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal secretion, suggest potential therapeutic benefits for diabetes.
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spelling pubmed-46396302015-11-27 Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics Li, Junfeng Zhang, Zhaoyun Liu, Xiaoxia Wang, Yi Mao, Fei Mao, Junjun Lu, Xiaolan Jiang, Dongdong Wan, Yun Lv, Jia-Ying Cao, Guoying Zhang, Jing Zhao, Naiqing Atkinson, Mark Greiner, Dale L. Prud'homme, Gerald J. Jiao, Zheng Li, Yiming Wang, Qinghua Front Pharmacol Pharmacology Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of type 1 diabetes. Because little is known about its absorption and effects in humans, we investigated the pharmacokinetics and pharmacodynamics of GABA in healthy volunteers. Twelve subjects were subjected to an open-labeled, three-period trial involving sequential oral administration of placebo, 2 g GABA once, and 2 g GABA three times/day for 7 days, with a 7-day washout between each period. GABA was rapidly absorbed (Tmax: 0.5 ~ 1 h) with the half-life (t1/2) of 5 h. No accumulation was observed after repeated oral GABA administration for 7 days. Remarkably, GABA significantly increased circulating insulin levels in the subjects under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p < 0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p < 0.01). GABA also increased glucagon levels only under fasting conditions (1.3-fold, single dose, p < 0.05; 1.5-fold, repeated dose, p < 0.01). However, there were no significant differences in the insulin-to-glucagon ratio and no significant change in glucose levels in these healthy subjects during the study period. Importantly, GABA significantly decreased glycated albumin levels in the repeated dosing period. Subjects with repeated dosing showed an elevated incidence of minor adverse events in comparison to placebo or the single dosing period, most notably transient discomforts such as dizziness and sore throat. However, there were no serious adverse events observed throughout the study. Our data show that GABA is rapidly absorbed and tolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal secretion, suggest potential therapeutic benefits for diabetes. Frontiers Media S.A. 2015-11-10 /pmc/articles/PMC4639630/ /pubmed/26617516 http://dx.doi.org/10.3389/fphar.2015.00260 Text en Copyright © 2015 Li, Zhang, Liu, Wang, Mao, Mao, Lu, Jiang, Wan, Lv, Cao, Zhang, Zhao, Atkinson, Greiner, Prud'homme, Jiao, Li and Wang. http://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) or licensor 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
Li, Junfeng
Zhang, Zhaoyun
Liu, Xiaoxia
Wang, Yi
Mao, Fei
Mao, Junjun
Lu, Xiaolan
Jiang, Dongdong
Wan, Yun
Lv, Jia-Ying
Cao, Guoying
Zhang, Jing
Zhao, Naiqing
Atkinson, Mark
Greiner, Dale L.
Prud'homme, Gerald J.
Jiao, Zheng
Li, Yiming
Wang, Qinghua
Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics
title Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics
title_full Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics
title_fullStr Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics
title_full_unstemmed Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics
title_short Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics
title_sort study of gaba in healthy volunteers: pharmacokinetics and pharmacodynamics
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639630/
https://www.ncbi.nlm.nih.gov/pubmed/26617516
http://dx.doi.org/10.3389/fphar.2015.00260
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