Effects Of Gamma-aminobutyric Acid Research Articles

Adding gamma-aminobutyric acid to modulate the in vitro digestive characteristics of tapioca pearls

The effects of gamma-aminobutyric acid (GABA) on gelatinization, pasting and rheological properties of the blend of hydroxypropyl distarch phosphate and tapioca starch were studied to examine the in vitro digestive characteristics of tapioca pearls. The addition of higher GABA contents resulted in lower starch hydrolysis rates and release rates of GABA during the digestion process, which indicated that GABA could modulate the digestive properties of tapioca pearls. RVA and DSC results showed that GABA inhibited the gelatinization of mixed starch and hindered the recrystallization of starch, leading to enhanced thermal stability and reduced viscosity. Also, the addition of GABA limited the water absorption and expansion of starch to some extent, resulting in decreased elastic and viscous moduli. XRD results showed that GABA changed the crystal structure of original mixed starch with reduced crystallinity. Moreover, the addition of GABA resulted in a reduction of RDS content and a significant increase in RS, which would provide potential applications for GABA in starchy health food.

Benzodiazepines Reduce Blood Pressure in Short Term: A Systematic Review and Meta-analysis.

Benzodiazepines, due to their anxiolytic properties, are prescribed to reduce anxiety and insomnia. They might have hypotensive effect via potentiation of the inhibitory effect of gamma-amino butyric acid (GABA) in the central nervous system and vasodilatory properties. However, studies comparing the effect of benzodiazepines in lowering blood pressure (BP) are equivocal. This systematic review and meta-analysis was planned to assess the efficacy of benzodiazepines in reducing blood pressure in short term among hypertensive patients. Various trials and retrospective analysis conducted previously have reported that benzodiazepines cause short- as well as long-term BP reduction in patients with increased anxiety with hypertension. On the other hand, several studies investigating the efficacy of benzodiazepines in patients with hypertension have reported inconclusive results. The primary question about the effect of benzodiazepines in lowering BP remains unanswered. In this meta-analysis of seven studies, benzodiazepines were found comparable to standard drugs in reducing systolic and diastolic BP in patients having hypertension. Although, the mean difference in systolic BP with benzodiazepines and placebo was statistically not significant, the difference can be considered as clinically meaningful. The current review offers preliminary evidence that benzodiazepines may have antihypertensive properties and may be used as add-on antihypertensive in a subset of patients in short term. The existing data are encouraging, but more clinical trials and mechanistic research are required to ascertain the long-term benefits.

What are the effects of gamma-aminobutyric acid (GABA) analogs or kappa-opioid agonists for adults with uremic pruritus?

What are the effects of gamma-aminobutyric acid (GABA) analogs or kappa-opioid agonists for adults with uremic pruritus?

Evaluation of yield and water use efficiency of quinoa under irrigation regimes, gamma aminobutyric acid, and vermicompost application

The current study was aim to evaluate the interaction effects of gamma aminobutyric acid (GABA) and vermicompost on yield and yield components of quinoa under different levels of drought stress. For this, two experiments were similarly designed as the factorial-split with four replicates for evaluating this hypothesis. Irrigation regimes (50, 75, and 100 % of plant water requirement (PWR)) as the main plot and vermicompost V (0, 5 t ha-1) × gamma aminobutyric acid GABA levels (0, 5, 10 mg l-1) as the subplot were designed. Severe drought stress had a significant effect on plant height. Plant height reduced 31.8 % after using 50 % of PWR compared to the control conditions. Although drought stress negatively affected the 1000 seed mass and seed yield, GABA foliar application alleviated these effects. After using 50 % of PWR, 10 mg l-1 of GABA increased the seed yield and harvest index up to 21.22 and 15.5 %, respectively, compared to the non-foliar application. The reduction in PWR from 100 to 50 % led to increasing in P and K concentrations, as well as sugar and proline contents. In the same conditions, the use of GABA or V had a significant effect on improving these traits. A similar trend was also recorded in relation to water use efficiency. Therefore, using 10 mg l-1 of GABA and 5 t ha-1 of V can be effective in alleviating water stress.

Effect of gamma-aminobutyric acid on resistance against stripe rust (caused by Puccinia striiformis f. sp. tritici) in wheat cultivars

Aim: The present study was undertaken to screen wheat cultivars for resistance against stripe rust and the improvement of resistance by exogenous gamma-aminobutyric acid (GABA) under field conditions and studying two contrasting cultivars for antioxidant related defense activities at 1, 2 and 4 d of GABA, Puccinia striiformis f. sp. tritici (Pst) and GABA+Pst treatments given to one-month-old seedlings. Methodology: Wheat cultivars (PBW723, PBW725, PBW677, PBW550, PBW343, PBW621, HD2967) were grown and exposed to Puccinia striiformis f. sp. tritici (Pst) and GABA+Pst in fields and studied for yield parameters. Subsequently, two cultivars found varying in resistance (PBW725 and HD2967) were analyzed for antioxidant enzymes in leaves and roots at 1, 2, and 4 day of GABA, Pst, and GABA+Pst and water as control given to 30 days old seedlings in the greenhouse. Results: Field analysis found that the most resistant cultivar PBW725 reduced vegetative growth but not yield compared to other resistant cultivars (PBW723 and PBW677) under Pst and improved both growth and yield under GABA+Pst. GABA+Pst improved yield parameters in other cultivars also. In defense analysis, superoxide dismutase (SOD), ascorbate peroxidase (APX) and glutathione-S-transferase (GST) increased in the leaves of PBW725 while only APX increased in HD2967 at 1 d of Pst. In roots also, SOD and GST increased 2-fold in PBW725 while only GST increased 1.3-fold in HD2967 at 1 d of Pst. There was persistence of catalase (CAT), monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase (DHAR) during Pst in the leaves of PBW 725 while CAT decreased at 4 d in HD2967. In roots also, CAT and MDHAR increased at 4 days of Pstin PBW725 while DHAR decreased in HD2967. Under GABA, cultivar differences were not significant. GABA+Pst improved deficient antioxidant enzymes in HD2967. Interpretation: Energy conservation and timely regulation of antioxidant enzymes during infection was utilized by PBW725 against stripe rust. GABA deficiency can be a reason for poor regulation of antioxidants in HD2967 under Pst. GABA application improved resistance against stripe rust in wheat. Key words: Antioxidant, Ascorbate, Gamma-aminobutyric acid, Glutathione, Stripe rust, Triticum aestivum

Effects of gamma aminobutyric acid on performance, blood cell of broiler subjected to multi-stress environments.

Stress factors such as high temperatures, overcrowding, and diurnal temperature range exert profound negative effects on weight gain and productivity of broiler chickens. The potential of gamma aminobutyric acid (GABA) as an excitatory neurotransmitter was evaluated under various stress conditions in this study. The experiment was conducted under four different environmental conditions: normal, high temperature, overcrowded, and in an overcrowded-diurnal temperature range. The experimental groups were divided into (-) control group without stress, (+) control group with stress, and G50 group (GABA 50 mg/kg) with stress. Weight gain, feed intake, and feed conversion ratio were measured, and stress reduction was evaluated through hematologic analysis. The effects of GABA on broilers in four experimental treatments were evaluated. GABA treated responded to environmental stress and improved productivity in all the experimental treatments. The magnitude of stress observed was highest at high temperature, followed by the overcrowded environment, and was least for the overcrowded-diurnal temperature range. Various stress factors in livestock rearing environment can reduce productivity and increase disease incidence and mortality rate. To address these challenges, GABA, an inhibitory neurotransmitter, was shown to reduce stress caused due to various environmental conditions and improve productivity.

Gamma-amino butyric acid (GABA) supplementation alleviates dexamethasone treatment-induced oxidative stress and inflammation response in broiler chickens

This experiment was conducted to investigate the effect of Gamma-amino butyric acid (GABA) on growth performance, serum and liver antioxidant status, inflammation response and hematological changes, in male broiler chickens under experimentally induced stress via in-feed dexamethasone (DEX). A total of 300 male chicks (Ross 308) on day 7 after hatching, were randomly selected into four groups which were positive control group (PC, without any treatment), negative control (NC, with 1 mg/kg DEX), a third group received 1 mg/kg DEX and 100 mg/kg GABA (DG +) and the last one was (DG ++) which received 1 mg/kg DEX and 200 mg/kg GABA. Each group has five replicates (15 birds/replicate). Dietary GABA modulated DEX-induced adverse effects on body weight, feed intake, and feed conversion ratio. The DEX-induced effect of serum levels of IL-6 and IL-10 was reduced by dietary GABA supplementation. The activity of serum and liver superoxide dismutase, catalase, glutathione peroxidase were enhanced and malondialdehyde was reduced by GABA supplementation. The serum levels of total cholesterol & triglyceride were higher while low-density lipoprotein & high-density lipoprotein were lower in GABA groups than NC group. GABA supplementation also significantly decreased the heterophil, heterophil/lymphocyte ratio and elevated the activities of aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) than NC group. In conclusion, dietary GABA supplementation can alleviate DEX stress-induced oxidative stress and inflammation response.

Interaction of Gamma-Aminobutyric Acid and Ca2+ on Phenolic Compounds Bioaccumulation in Soybean Sprouts under NaCl Stress.

NaCl stress can enhance the accumulation of phenolic compounds in soybean during germination. In the present study, effects of gamma-aminobutyric acid (GABA) and Ca2+ on the biosynthesis of phenolic compounds in soybean sprouts germinated with NaCl stress were investigated. Results showed that addition of Ca2+ increased the content of total phenolics, phenolic acids, and isoflavonoids in soybean sprouts by ca. 15%, 7%, and 48%, respectively, through enhancing the activities of three key enzymes involved in the biosynthesis. On the other hand, addition of LaCl3, a calcium channel blocker, inhibited the synthesis of phenolic compounds, indicating that Ca2+ plays an important role in the synthesis of these compounds in soybean sprouts. Addition of GABA can increase the content of Ca2+ in soybean sprouts by ca. 20% and alleviate the inhibition of LaCl3 on phenolics biosynthesis in soybean sprouts. Similarly, addition of Ca2+ can reverse the inhibition of 3-mercaptopropionate, an inhibitor of endogenous GABA synthesis, on the biosynthesis of phenolic compounds in soybean sprouts under NaCl stress. To conclude, both GABA and Ca2+ can enhance the biosynthesis of phenolic compounds in soybean sprouts and there was an interaction between their effects on the promotion of phenolic compounds biosynthesis.

The Effect of GABA on the Gut Microbiota During Metabolic Stress

The effect of gamma-aminobutyric acid (GABA) on the gut microbiota was evaluated in experiments on 47 rats with metabolic stress (MS) induced by food deprivation. MS was found to be associated with changes in the qualitative and quantitative composition of the caecum microbiota, including the redistribution of opportunistic flora, the growth of pathogenic microorganisms, as well as a decreased number of lactobacilli and bifidobacteria. Daily administration of GABA at a dose of 70 mg/kg during MS led to a decrease in the number of pathogens, thus leading to the restoration of normal eubionts in the cecum.

The protective effect of gamma aminobutyric acid B receptor activation on sympathetic nerve remodeling via the regulation of M2 macrophage polarization after myocardial infarction

Introduction & objectivesAcute myocardial infarction (AMI) in coronary heart disease is a leading cause of sudden death primarily due to malignant ventricular arrhythmias (VAs). Inflammatory cell infiltration and inflammation-induced overactivation of sympathetic nerves are the major cause of VAs in AMI pathophysiological processes. Type 2 macrophages play an anti-inflammatory role in AMI. Targeting macrophages may be a therapeutic strategy to prevent VAs post AMI. We found that gamma aminobutyric acid (GABA) promotes macrophages polarized to M2 and hypothesized that GABA might exert anti-inflammatory effects by promoting type 2 macrophage polarization in AMI. We aim to characterized GABAB receptor distribution, function, and mechanisms in M2 macrophage polarization and explored the functional aspect of GABAB receptor activation in sympathetic remodeling. ResultsGamma aminobutyric acid B receptors were expressed on macrophage surface both in vitro and in vivo. GABAB receptor agonist baclofen, GABA promoted macrophage switch to M2. While GABAB receptor antagonist CGP52432 blocked a baclofen induced switch to M2 polarization. GABA and baclofen increased M2 macrophage percentage and CGP52432 blocked this process in vivo. Also, IL-10 and TGF-β1 released by M2 were increased in both AMI and baclofen/AMI group; Serum NE levels were decreased by baclofen. All the above effects were reversed by CGP52432 treatment. Baclofen decreased TH and GAP-43 staining while CGP52432 enhanced their expression post AMI indicating GABAB receptor activation inhibited sympathetic nerve sprouting and activity by reducing NE release. ConclusionsGamma aminobutyric acid B receptor activation promoted M2 polarization and protested AMI heart by regulating sympathetic nerve remodeling.

Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity.

Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternative to traditional salt on aggravated renal injury by high salt intake in cisplatin-induced nephrotoxicity mice. High salt intake accelerated the increase of biomarkers, such as blood urea nitrogen and serum creatinine levels for renal injury in cisplatin-induced nephrotoxicity mice. However, oral administration of GABA-contained salt notably suppressed serum BUN and creatinine levels. The efficacy of GABA salt was superior to lacto GABA salt and postbiotics GABA salt. Furthermore, GABA-enriched salt markedly restored histological symptoms of nephrotoxicity including renal hypertrophy, tubular dilation, hemorrhage, and collagen deposition aggravated by salt over-loading in cisplatin-exposed mice. Among them, GABA salt showed a higher protective effect against cisplatin-induced renal histological changes than lacto GABA salt and postbiotics GABA salt. In addition, administration of high salt significantly enhanced expression levels of apoptosis and inflammatory mediators in cisplatin-induced nephrotoxicity mice, while GABA-enriched salt greatly down-regulated the expression of these mediators. Taken together, these results demonstrate the protective effect of GABA against damage caused by high salt intake in cisplatin-induced renal toxicity. Its mechanism may be due to the suppression of hematological and biochemical toxicity, apoptosis, and inflammation. In conclusion, although the protective efficacy of GABA salt on renal injury is different depending on the sterilization and filtration process after fermentation with L. brevis BJ20 and L. plantarum BJ21, our findings suggest that GABA-enriched salt has a beneficial effect against immoderate high salt intake-mediated kidney injury in patients with cisplatin-induced nephrotoxicity.

Vase life and antioxidant status of two carnations (Dianthus caryophyllus L.) cultivars affected by gamma aminobutyric acid (GABA) treatments

Purpose: Carnation (Dianthus caryophyllus L.) is one of the most popular and economically important cut flowers worldwide ranking the third after rose and chrysanthemum. The vase life of many carnation cultivars is short due to sensitivity to ethylene or other factors. This research was performed to study effect of gamma aminobutyric acid (GABA 0.5, 0.75 and 1mM) on postharvest quality of tow famous carnation cultivars viz. Delphi (white) and Dob Pedro (Red). Research method: The experiment was conducted as completely randomized design (CRD) with five replications per treatment. Findings: The results indicated that all concentrations of GABA significantly prolonged the vase life in both cultivars. GABA decreased lipid peroxidation of petal tissue while increased the activity of some antioxidant enzymes such as catalase (CAT), ascorbate peroxidase (APX), superoxide dismutase (SOD) and guaiacol peroxidase (GPX). Polyphenoloxidase (PPO) activity was also decreased in GABA-treated cut flower. Interestingly, both cultivars responded similarly to GABA treatments. The findings also revealed that GABA had antioxidant properties capable of increasing defense ability of the carnation cut flower. Meanwhile, the applied concentration is very critical and should be taken into account. Based on the present findings, the best treatment is GABA at 0.75 mM. Limitations: No limitations were encountered. Originality/Value: The results of this research indicated that GABA had antioxidant properties capable of increasing defense ability of the carnation cut flower. It appears that the applied GABA operates through membrane conservation, increasing the activity of antioxidants enzymes and decreasing PPO activity.

An association study in the Taiwan Biobank elicits the GABAA receptor genes GABRB3, GABRA5, and GABRG3 as candidate loci for sleep duration in the Taiwanese population

BackgroundGamma-aminobutyric acid type A (GABAA) receptors mainly mediate the effects of gamma-aminobutyric acid, which is the primary inhibitory neurotransmitter in the central nervous system. Abundant evidence suggests that GABAA receptors play a key role in sleep-regulating processes. No genetic association study has explored the relationships between GABAA receptor genes and sleep duration, sleep quality, and sleep timing in humans.MethodsWe determined the association between single-nucleotide polymorphisms (SNPs) in the GABAA receptor genes GABRA1, GABRA2, GABRB3, GABRA5, and GABRG3 and sleep duration, sleep quality, and sleep timing in the Taiwan Biobank with a sample of 10,127 Taiwanese subjects. There were 10,142 subjects in the original study cohort. We excluded 15 subjects with a medication history of sedative-hypnotics.ResultsOur data revealed an association of the GABRB3-GABRA5-GABRG3 gene cluster with sleep duration, which has not been previously identified: rs79333046 (beta = − 0.07; P = 1.21 × 10–3) in GABRB3, rs189790076 (beta = 0.92; P = 1.04 × 10–3) in GABRA5, and rs147619342 (beta = − 0.72; P = 3.97 × 10–3) in GABRG3. The association between rs189790076 in GABRA5 and sleep duration remained significant after Bonferroni correction. A variant (rs12438141) in GABRB3 was also found to act as a potential expression quantitative trait locus. Additionally, we discovered interactions between variants in the GABRB3-GABRA5-GABRG3 gene cluster and lifestyle factors, such as tea and coffee consumption, smoking, and physical activity, that influenced sleep duration, although some interactions became nonsignificant after Bonferroni correction. We also found interactions among GABRB3, GABRA5, and GABRG3 that affected sleep duration. Furthermore, we identified an association of rs7165524 (beta = − 0.06; P = 2.20 × 10–3) in GABRA5 with sleep quality and an association of rs79465949 (beta = − 0.12; P = 3.95 × 10–3) in GABRB3 with sleep timing, although these associations became nonsignificant after Bonferroni correction. However, we detected no evidence of an association of individual SNPs in GABRA1 and GABRA2.ConclusionsOur results indicate that rs189790076 in GABRA5 and gene–gene interactions among GABRB3, GABRA5, and GABRG3 may contribute to sleep duration in the Taiwanese population.

Effects of Gamma-Aminobutyric Acid on Seed Germination, Ion Balance, and Metabolic Activity in Perennial Ryegrass Under Salinity Stress

Effects of Gamma-Aminobutyric Acid on Seed Germination, Ion Balance, and Metabolic Activity in Perennial Ryegrass Under Salinity Stress

Gamma-amino butyric acid effect in the alleviation of saline–alkaline stress conditions in rice

The present study was conducted in order to determine the effect of GABA on 2 rice cultivars, i.e., CSR 43 (tolerant) and Pusa 44 (susceptible) at seedling stage under 200 mM saline–alkaline stress (SAS) (molar ratio of 1:9:9:1 of NaCl/Na2SO4/Na2CO3/Na2HCO3) with and without GABA (1.5 mM) supplementation. Exogenous GABA application enhanced the protein content along with the activities of glutamate decarboxylase (GAD) and diamine oxidase (DAO) in cultivar CSR 43. Under SAS, the activities of GAD, DAO and contents of protein were found higher in CSR 43 as compared to Pusa 44 while reverse was observed under GABA + SAS. As compared to sole application of GABA/SAS, CSR 43 possessed higher proline content under GABA + SAS. Endogenous GABA contents were found to increase under SAS in both cultivars, whereas the levels remained higher in CSR 43. Thus, it is elucidated that the increased endogenous GABA by exogenous GABA treatment could improve stress tolerance of rice seedlings associated with GABA regulation in improving DAO activity along with proline content.

Stress-Induced Alteration in Chloride Transporters in the Trigeminal Nerve May Explain the Comorbidity between Depression and Migraine

Migraine is frequently comorbid with depression and anxiety disorders. In the case of depression and panic disorder, the associations seem to be bidirectional. Stress (activation of the hypothalamic-pituitary-adrenal axis) is thought to be involved in increasing the attack frequency. In the current review, it is argued that elevated levels of cortisol increase the function of chloride-ion transporter NKCC1 and decrease the function of chloride-extruder KCC2 in the trigeminal nerve. This leads to a diminished inhibitory effect of gamma-aminobutyric acid (GABA) and an enhanced likelihood of a migraine attack. Since migraine attacks themselves are stressful, and since brain areas are activated that could contribute to panic, anxiety and depression, a number of self-sustaining circular processes could occur that would explain the bi-directionality of the associations. On the basis of this hypothesis, several novel therapeutic approaches to counter the pathological process can be proposed. These include inhibition of corticotrophin releasing factor by CRF1 receptor antagonists, blockade of adrenocorticotropic hormone (ACTH) at the MC2 receptor, and inhibition of the hyperactive NKCC1 chloride-transporter.

Effects of gamma-aminobutyric acid and piperine on gene regulation in pig kidney epithelial cell lines.

ObjectiveGamma-aminobutyric acid (GABA) and piperine (PIP) are both nutritional supplements with potential use in animal diets. The purpose of this study is to investigate the effect of GABA and/or PIP treatment on the gene expression pattern of a pig kidney epithelial cell line.MethodsLLCPK1 cells were treated with GABA, PIP, or both, and then the gene expression pattern was analyzed using microarray. Gene ontology analysis was done using GeneOntology (Geneontology.org), and validation was performed using quantitative real-time polymerase chain reaction.ResultsGene ontology enrichment analysis was used to identify key pathway(s) of genes whose expression levels were regulated by these treatments. Microarray results showed that GABA had a positive effect on the transcription of genes related to regulation of erythrocyte differentiation and that GABA and PIP in combination had a synergistic effect on genes related to immune systems and processes. Furthermore, we found that effects of GABA and/or PIP on these selected genes were controlled by JNK/p38 MAPK pathway.ConclusionThese results can improve our understanding of mechanisms involved in the effect of GABA and/or PIP treatment on pig kidney epithelial cells. They can also help us evaluate their potential as a clinical diagnosis and treatment.

The Effect of Gamma Aminobutyric Acid and Ascorbic Acid on Bali Cattle Physiology During Transport

The Effect of Gamma Aminobutyric Acid and Ascorbic Acid on Bali Cattle Physiology During Transport

Gamma-aminobutyric acid decreases macrophages infiltration and suppresses inflammatory responses in renal injury

Abstract The immunomodulatory effects of gamma-aminobutyric acid (GABA) on renal disease were investigated using conditional von Hippel-Lindau gene-knockout C57BL/6 mice (Vhlhdel/del mice), which spontaneously develop fibrosis, inflammation, and hyperplastic clear-cell lesions in the kidneys. Diets containing either GABA rice or pure GABA significantly extended the life span of Vhlhdel/del mice, with decreasing levels of urinary kidney injury molecule (KIM)-1 and renal clear cell formation, which are the typical markers of renal damage. Levels of serum inflammatory markers such as interleukin (IL)-6, renal monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-β, IL-17A, C-C chemokine receptor type 2 (CCR2), and macrophage infiltration were significantly decreased in GABA-fed mice. Further, induction of monocyte migration was significantly suppressed in GABA-treated VHL-silenced HK-2 cells, suggesting that GABA has protective effects against renal injury by disrupting the MCP-1/CCR2 axis and thus macrophage infiltration.

Effect of gamma aminobutyric acid (GABA) or GABA with glutamic acid decarboxylase (GAD) on the progression of type 1 diabetes mellitus in children: Trial design and methodology

BackgroundEvidence suggests that GABA may reduce pancreatic inflammation, protect β-cells from autoimmune destruction, and potentiate the regeneration of new β-cells in the setting of type 1 diabetes mellitus (T1DM). The enzyme GAD, also expressed in human pancreatic β-cells, is an antigenic target of reactive T cells. We hypothesized that treatment of children with recent onset T1DM with GABA or combination GABA with GAD will preserve β-cell function and ameliorate autoimmune dysregulation. MethodsThis is a one-year, prospective, randomized, double-blind, placebo-controlled trial. Ninety-nine patients aged 4–18 years with newly diagnosed T1DM are randomized into three treatment groups: 1) oral GABA twice daily in addition to two injections of recombinant GAD enzyme, 2) oral GABA plus placebo GAD injections, or 3) placebo GABA and placebo GAD. Patients are evaluated at baseline and months 1, 5, 8 and 12. Mixed meal tolerance testing is performed at all but the 8-month visit. Laboratory studies will assess indices of beta and alpha cell function, glycemic control, immunophenotyping, and diabetes-related autoantibodies. ResultsThe primary outcome is the effect on pancreatic β-cell function as measured by meal-stimulated c-peptide secretion compared between the treatment groups before and after one year of treatment. Secondary outcomes include: 1) fasting and meal stimulated glucagon and proinsulin levels, 2) response in insulin usage by participants, 3) indices of immune cell function, and 4) effect on autoantibodies GAD65, ICA512, and ZnT8.Conclusions: This trial will determine the safety and efficacy of GABA and combination GABA/GAD therapy to delay T1DM progression in children.