Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 Diabetes
Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system (CNS) and outside of the CNS, found in the highest concentrations in immune cells and pancreatic beta-cells. GABA is gaining increasing interest in diabetes research due to its immune-modulatory...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/1/91 |
| _version_ | 1797495603635159040 |
|---|---|
| author | Henrik Hill Andris Elksnis Per Lundkvist Kumari Ubhayasekera Jonas Bergquist Bryndis Birnir Per-Ola Carlsson Daniel Espes |
| author_facet | Henrik Hill Andris Elksnis Per Lundkvist Kumari Ubhayasekera Jonas Bergquist Bryndis Birnir Per-Ola Carlsson Daniel Espes |
| author_sort | Henrik Hill |
| collection | DOAJ |
| description | Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system (CNS) and outside of the CNS, found in the highest concentrations in immune cells and pancreatic beta-cells. GABA is gaining increasing interest in diabetes research due to its immune-modulatory and beta-cell stimulatory effects and is a highly interesting drug candidate for the treatment of type 1 diabetes (T1D). GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD), one of the targets for autoantibodies linked to T1D. Using mass spectrometry, we have quantified the endogenous circulating levels of GABA in patients with new-onset and long-standing T1D and found that the levels are unaltered when compared to healthy controls, i.e., T1D patients do not have a deficit of systemic GABA levels. In T1D, GABA levels were negatively correlated with IL-1 beta, IL-12, and IL-15 15 and positively correlated to levels of IL-36 beta and IL-37. Interestingly, GABA levels were also correlated to the levels of GAD-autoantibodies. The unaltered levels of GABA in T1D patients suggest that the GABA secretion from beta-cells only has a minor impact on the circulating systemic levels. However, the local levels of GABA could be altered within pancreatic islets in the presence of GAD-autoantibodies. |
| first_indexed | 2024-03-10T01:52:01Z |
| format | Article |
| id | doaj.art-7623d43e37e248ffa239e06a46b71a94 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T01:52:01Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-7623d43e37e248ffa239e06a46b71a942023-11-23T13:03:39ZengMDPI AGBiomedicines2227-90592021-12-011019110.3390/biomedicines10010091Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 DiabetesHenrik Hill0Andris Elksnis1Per Lundkvist2Kumari Ubhayasekera3Jonas Bergquist4Bryndis Birnir5Per-Ola Carlsson6Daniel Espes7Department of Women’s and Children’s Health, Uppsala University, 75185 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Sciences, Uppsala University, 75309 Uppsala, SwedenDepartment of Chemistry, Analytical, BMC, Uppsala University, 75237 Uppsala, SwedenDepartment of Chemistry, Analytical, BMC, Uppsala University, 75237 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenScience for Life Laboratory, Department of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenGamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system (CNS) and outside of the CNS, found in the highest concentrations in immune cells and pancreatic beta-cells. GABA is gaining increasing interest in diabetes research due to its immune-modulatory and beta-cell stimulatory effects and is a highly interesting drug candidate for the treatment of type 1 diabetes (T1D). GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD), one of the targets for autoantibodies linked to T1D. Using mass spectrometry, we have quantified the endogenous circulating levels of GABA in patients with new-onset and long-standing T1D and found that the levels are unaltered when compared to healthy controls, i.e., T1D patients do not have a deficit of systemic GABA levels. In T1D, GABA levels were negatively correlated with IL-1 beta, IL-12, and IL-15 15 and positively correlated to levels of IL-36 beta and IL-37. Interestingly, GABA levels were also correlated to the levels of GAD-autoantibodies. The unaltered levels of GABA in T1D patients suggest that the GABA secretion from beta-cells only has a minor impact on the circulating systemic levels. However, the local levels of GABA could be altered within pancreatic islets in the presence of GAD-autoantibodies.https://www.mdpi.com/2227-9059/10/1/91type 1 diabetesGABAislets of Langerhans GAD-autoantibodies |
| spellingShingle | Henrik Hill Andris Elksnis Per Lundkvist Kumari Ubhayasekera Jonas Bergquist Bryndis Birnir Per-Ola Carlsson Daniel Espes Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 Diabetes Biomedicines type 1 diabetes GABA islets of Langerhans GAD-autoantibodies |
| title | Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 Diabetes |
| title_full | Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 Diabetes |
| title_fullStr | Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 Diabetes |
| title_full_unstemmed | Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 Diabetes |
| title_short | Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 Diabetes |
| title_sort | endogenous levels of gamma amino butyric acid are correlated to glutamic acid decarboxylase antibody levels in type 1 diabetes |
| topic | type 1 diabetes GABA islets of Langerhans GAD-autoantibodies |
| url | https://www.mdpi.com/2227-9059/10/1/91 |
| work_keys_str_mv | AT henrikhill endogenouslevelsofgammaaminobutyricacidarecorrelatedtoglutamicaciddecarboxylaseantibodylevelsintype1diabetes AT andriselksnis endogenouslevelsofgammaaminobutyricacidarecorrelatedtoglutamicaciddecarboxylaseantibodylevelsintype1diabetes AT perlundkvist endogenouslevelsofgammaaminobutyricacidarecorrelatedtoglutamicaciddecarboxylaseantibodylevelsintype1diabetes AT kumariubhayasekera endogenouslevelsofgammaaminobutyricacidarecorrelatedtoglutamicaciddecarboxylaseantibodylevelsintype1diabetes AT jonasbergquist endogenouslevelsofgammaaminobutyricacidarecorrelatedtoglutamicaciddecarboxylaseantibodylevelsintype1diabetes AT bryndisbirnir endogenouslevelsofgammaaminobutyricacidarecorrelatedtoglutamicaciddecarboxylaseantibodylevelsintype1diabetes AT perolacarlsson endogenouslevelsofgammaaminobutyricacidarecorrelatedtoglutamicaciddecarboxylaseantibodylevelsintype1diabetes AT danielespes endogenouslevelsofgammaaminobutyricacidarecorrelatedtoglutamicaciddecarboxylaseantibodylevelsintype1diabetes |