The role of GABA in type 1 diabetes

Gamma aminobutyric acid (GABA) is synthesized from glutamate by glutamic decarboxylase (GAD). The entero-pancreatic biology of GABA, which is produced by pancreatic islets, GAD-expressing microbiota, enteric immune cells, or ingested through diet, supports an essential physiologic role of GABA in th...

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Main Authors: Gail J. Mick, Kenneth L. McCormick
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2024.1453396/full
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author Gail J. Mick
Kenneth L. McCormick
author_facet Gail J. Mick
Kenneth L. McCormick
author_sort Gail J. Mick
collection DOAJ
description Gamma aminobutyric acid (GABA) is synthesized from glutamate by glutamic decarboxylase (GAD). The entero-pancreatic biology of GABA, which is produced by pancreatic islets, GAD-expressing microbiota, enteric immune cells, or ingested through diet, supports an essential physiologic role of GABA in the health and disease. Outside the central nervous system (CNS), GABA is uniquely concentrated in pancreatic β-cells. They express GAD65, which is a type 1 diabetes (T1D) autoantigen. Glutamate constitutes 10% of the amino acids in dietary protein and is preeminently concentrated in human milk. GABA is enriched in many foods, such as tomato and fermented cheese, and is an over-the-counter supplement. Selected microbiota in the midgut have the enzymatic capacity to produce GABA. Intestinal microbiota interact with gut-associated lymphoid tissue to maintain host defenses and immune tolerance, which are implicated in autoimmune disease. Although GABA is a widely known inhibitory neurotransmitter, oral GABA does not cross the blood brain barrier. Three diabetes-related therapeutic actions are ascribed to GABA, namely, increasing pancreatic β-cell content, attenuating excess glucagon and tamping down T-cell immune destruction. These salutary actions have been observed in numerous rodent diabetes models that usually employed high or near-continuous GABA doses. Clinical studies, to date, have identified positive effects of oral GABA on peripheral blood mononuclear cell cytokine release and plasma glucagon. Going forward, it is reassuring that oral GABA therapy has been well-tolerated and devoid of serious adverse effects.
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spelling doaj-art-e7055b6d68744cddb40e8d2612c019fd2024-11-15T04:39:00ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-11-011510.3389/fendo.2024.14533961453396The role of GABA in type 1 diabetesGail J. MickKenneth L. McCormickGamma aminobutyric acid (GABA) is synthesized from glutamate by glutamic decarboxylase (GAD). The entero-pancreatic biology of GABA, which is produced by pancreatic islets, GAD-expressing microbiota, enteric immune cells, or ingested through diet, supports an essential physiologic role of GABA in the health and disease. Outside the central nervous system (CNS), GABA is uniquely concentrated in pancreatic β-cells. They express GAD65, which is a type 1 diabetes (T1D) autoantigen. Glutamate constitutes 10% of the amino acids in dietary protein and is preeminently concentrated in human milk. GABA is enriched in many foods, such as tomato and fermented cheese, and is an over-the-counter supplement. Selected microbiota in the midgut have the enzymatic capacity to produce GABA. Intestinal microbiota interact with gut-associated lymphoid tissue to maintain host defenses and immune tolerance, which are implicated in autoimmune disease. Although GABA is a widely known inhibitory neurotransmitter, oral GABA does not cross the blood brain barrier. Three diabetes-related therapeutic actions are ascribed to GABA, namely, increasing pancreatic β-cell content, attenuating excess glucagon and tamping down T-cell immune destruction. These salutary actions have been observed in numerous rodent diabetes models that usually employed high or near-continuous GABA doses. Clinical studies, to date, have identified positive effects of oral GABA on peripheral blood mononuclear cell cytokine release and plasma glucagon. Going forward, it is reassuring that oral GABA therapy has been well-tolerated and devoid of serious adverse effects.https://www.frontiersin.org/articles/10.3389/fendo.2024.1453396/fullgamma aminobutyric acid (GABA)Type 1 diabetesGABA treatment/diabetesβ-cells/pancreatic isletsα-cells/glucagondiabetes/new therapies
spellingShingle Gail J. Mick
Kenneth L. McCormick
The role of GABA in type 1 diabetes
Frontiers in Endocrinology
gamma aminobutyric acid (GABA)
Type 1 diabetes
GABA treatment/diabetes
β-cells/pancreatic islets
α-cells/glucagon
diabetes/new therapies
title The role of GABA in type 1 diabetes
title_full The role of GABA in type 1 diabetes
title_fullStr The role of GABA in type 1 diabetes
title_full_unstemmed The role of GABA in type 1 diabetes
title_short The role of GABA in type 1 diabetes
title_sort role of gaba in type 1 diabetes
topic gamma aminobutyric acid (GABA)
Type 1 diabetes
GABA treatment/diabetes
β-cells/pancreatic islets
α-cells/glucagon
diabetes/new therapies
url https://www.frontiersin.org/articles/10.3389/fendo.2024.1453396/full
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