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
“…It can depolarize the membrane potential of islet cells by activating GABA receptors (GABAbR) on the cell membrane to enhance insulin secretion and maintain glucose homeostasis (9). For instance, previous research confirmed that GABA can alleviate pancreatitis and autoimmune β-cell damage (10). Additionally, GABA can induce the transformation of α-cells to β-cells (11) and mediate the regeneration of β-like cells (12).…”
ObjectivesIn this study, the effects of γ-aminobutyric acid (GABA)-rich sprouted adzuki beans on the glycolipid metabolism and gastrointestinal health were investigated in mice with type 2 diabetes mellitus (T2DM).MethodsMice with T2DM were subjected to dietary intervention with different doses of GABA-rich sprouted adzuki beans for 6 consecutive weeks, during which growth indicators, glycolipid metabolism, and the composition and diversity of the gut microbiota changes were observed.ResultsA high dietary intake of GABA-rich sprouted adzuki beans had a preventive effect against weight gain, significantly reduced serum levels of FBG, TG, and TC. Additionally, high dietary intake of GABA-rich sprouted adzuki beans increased the abundances of Firmicutes, Bacteroidetes, Verrucomicrobia, and Akkermansia, leading to a shift in the structure of the gut microbiota toward the dominance of probiotics with regulatory effects on glycolipid metabolism.ConclusionsGABA-rich sprouted adzuki beans can effectively control the bodyweight of mice with T2DM, maintain a balanced blood glucose level, improve glycolipid metabolism and the changes in the microbiota may mediate the anti-diabetic effect of sprouted adzuki beans.
“…It can depolarize the membrane potential of islet cells by activating GABA receptors (GABAbR) on the cell membrane to enhance insulin secretion and maintain glucose homeostasis (9). For instance, previous research confirmed that GABA can alleviate pancreatitis and autoimmune β-cell damage (10). Additionally, GABA can induce the transformation of α-cells to β-cells (11) and mediate the regeneration of β-like cells (12).…”
ObjectivesIn this study, the effects of γ-aminobutyric acid (GABA)-rich sprouted adzuki beans on the glycolipid metabolism and gastrointestinal health were investigated in mice with type 2 diabetes mellitus (T2DM).MethodsMice with T2DM were subjected to dietary intervention with different doses of GABA-rich sprouted adzuki beans for 6 consecutive weeks, during which growth indicators, glycolipid metabolism, and the composition and diversity of the gut microbiota changes were observed.ResultsA high dietary intake of GABA-rich sprouted adzuki beans had a preventive effect against weight gain, significantly reduced serum levels of FBG, TG, and TC. Additionally, high dietary intake of GABA-rich sprouted adzuki beans increased the abundances of Firmicutes, Bacteroidetes, Verrucomicrobia, and Akkermansia, leading to a shift in the structure of the gut microbiota toward the dominance of probiotics with regulatory effects on glycolipid metabolism.ConclusionsGABA-rich sprouted adzuki beans can effectively control the bodyweight of mice with T2DM, maintain a balanced blood glucose level, improve glycolipid metabolism and the changes in the microbiota may mediate the anti-diabetic effect of sprouted adzuki beans.
Gamma aminobutyric acid(GABA) is synthesized by glutamate decarboxylase(GAD) in β-cells. Regarding Type 1 diabetes(T1D), animal/islet-cell studies found that GABA promotes insulin secretion, inhibits α-cell glucagon and dampens immune inflammation, while GAD immunization may also preserve β-cells. We evaluated the safety and efficacy of oral GABA alone, or combination GABA with GAD, on the preservation of residual insulin secretion in recent-onset T1D. Herein we report a single-center, double-blind, one-year, randomized trial in 97 children conducted March 2015 to June 2019(NCT02002130). Using a 2:1 treatment:placebo ratio, interventions included oral GABA twice-daily(n = 41), or oral GABA plus two-doses GAD-alum(n = 25), versus placebo(n = 31). The primary outcome, preservation of fasting/meal-stimulated c-peptide, was not attained. Of the secondary outcomes, the combination GABA/GAD reduced fasting and meal-stimulated serum glucagon, while the safety/tolerability of GABA was confirmed. There were no clinically significant differences in glycemic control or diabetes antibody titers. Given the low GABA dose for this pediatric trial, future investigations using higher-dose or long-acting GABA formulations, either alone or with GAD-alum, could be considered, although GABA alone or in combination with GAD-alum did nor preserve beta-cell function in this trial.
“…Furthermore, the activation of GABA(A) receptor has been shown to inhibit proliferation in T cells isolated from human peripheral blood mononuclear cells in vitro [ 106 ]. Based on these compelling data, clinical trials with GABA have been initiated for prevention and treatment for new onset T1DM; however, its safety and efficacy has not been reported thus far [ 107 ]. Lastly, GABA has been shown to improve insulin resistance through increasing peripheral expression of Glut4, reducing inflammation, and decreasing blood glucose levels [ 108 ].…”
Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia as a result of insufficient insulin levels and/or impaired function as a result of autoimmune destruction or insulin resistance. While Type 1 DM (T1DM) and Type 2 DM (T2DM) occur through different pathological processes, both result in β-cell destruction and/or dysfunction, which ultimately lead to insufficient β-cell mass to maintain normoglycemia. Therefore, therapeutic agents capable of inducing β-cell proliferation is crucial in treating and reversing diabetes; unfortunately, adult human β-cell proliferation has been shown to be very limited (~0.2% of β-cells/24 h) and poorly responsive to many mitogens. Furthermore, diabetogenic insults result in damage to β cells, making it ever more difficult to induce proliferation. In this review, we discuss β-cell mass/proliferation pathways dysregulated in diabetes and current therapeutic agents studied to induce β-cell proliferation. Furthermore, we discuss possible combination therapies of proliferation agents with immunosuppressants and antioxidative therapy to improve overall long-term outcomes of diabetes.
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