Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of\ntype 1 diabetes. Because little is known about its absorption and effects in humans,\nwe investigated the pharmacokinetics and pharmacodynamics of GABA in healthy\nvolunteers. Twelve subjects were subjected to an open-labeled, three-period trial\ninvolving sequential oral administration of placebo, 2 g GABA once, and 2 g GABA three\ntimes/day for 7 days, with a 7-day washout between each period. GABA was rapidly\nabsorbed (Tmax: 0.5 âË?¼ 1 h) with the half-life (t1/2) of 5 h. No accumulation was observed\nafter repeated oral GABA administration for 7 days. Remarkably, GABA significantly\nincreased circulating insulin levels in the subjects under either fasting (1.6-fold, single\ndose; 2.0-fold, repeated dose; p < 0.01) or fed conditions (1.4-fold, single dose;\n1.6-fold, repeated dose; p < 0.01). GABA also increased glucagon levels only under\nfasting conditions (1.3-fold, single dose, p < 0.05; 1.5-fold, repeated dose, p < 0.01).\nHowever, there were no significant differences in the insulin-to-glucagon ratio and no\nsignificant change in glucose levels in these healthy subjects during the study period.\nImportantly, GABA significantly decreased glycated albumin levels in the repeated dosing\nperiod. Subjects with repeated dosing showed an elevated incidence of minor adverse\nevents in comparison to placebo or the single dosing period, most notably transient\ndiscomforts such as dizziness and sore throat. However, there were no serious adverse\nevents observed throughout the study. Our data show that GABA is rapidly absorbed and\ntolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal\nsecretion, suggest potential therapeutic benefits for diabetes.
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