title: Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Zhaoyun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Mao
authors.affiliation: Department of Pharmacy, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Biostatistics, School of Public Health, Fudan University Shanghai, China.
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Lv
authors.affiliation: Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Cao
authors.affiliation: Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biostatistics, School of Public Health, Fudan University Shanghai, China.
authors.forename: Naiqing
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Pathology, College of Medicine, University of Florida Gainesville, FL, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Atkinson
authors.affiliation: Department of Molecular Medicine, University of Massachusetts Medical School Worcester, MA, USA.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, University of Toronto Toronto, ON, Canada.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Prud'homme
authors.affiliation: Department of Pharmacy, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Jiao
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University Shanghai, China ; Division of Endocrinology and Metabolism, The Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital Toronto, ON, Canada ; Department of Physiology and Medicine, University of Toronto ON, Canada.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wang
keywords: GABA; glucagon; glycated albumin; insulin; pharmacokinetics