The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/106572 https://doi.org/10.1371/journal.pone.0240907 |
Resumo: | Glucose metabolism is pivotal for energy and neurotransmitter synthesis and homeostasis, particularly in Glutamate and GABA systems. In turn, the stringent control of inhibitory/excitatory tonus is known to be relevant in neuropsychiatric conditions. Glutamatergic neurotransmission dominates excitatory synaptic functions and is involved in plasticity and excitotoxicity. GABAergic neurochemistry underlies inhibition and predicts impaired psychophysical function in diabetes. It has also been associated with cognitive decline in people with diabetes. Still, the relation between metabolic homeostasis and neurotransmission remains elusive. Two 3T proton MR spectroscopy studies were independently conducted in the occipital cortex to provide insight into inhibitory/excitatory homeostasis (GABA/Glutamate) and to evaluate the impact of chronic metabolic control on the levels and regulation (as assessed by regression slopes) of the two main neurotransmitters of the CNS in type 2 diabetes (T2DM) and type 1 diabetes (T1DM). Compared to controls, participants with T2DM showed significantly lower Glutamate, and also GABA. Nevertheless, higher levels of GABA/Glx (Glutamate+Glutamine), and lower levels of Glutamate were associated with poor metabolic control in participants with T2DM. Importantly, the relationship between GABA/Glx and HbA1c found in T2DM supports a relationship between inhibitory/excitatory balance and metabolic control. Interestingly, this neurometabolic profile was undetected in T1DM. In this condition we found strong evidence for alterations in MRS surrogate measures of neuroinflammation (myo-Inositol), positively related to chronic metabolic control. Our results suggest a role for Glutamate as a global marker of T2DM and a sensitive marker of glycemic status. GABA/Glx may provide a signature of cortical metabolic state in poorly controlled patients as assessed by HbA1c levels, which indicate long-term blood Glucose control. These findings are consistent with an interplay between abnormal neurotransmission and metabolic control in particular in type 2 diabetes thereby revealing dissimilar contributions to the pathophysiology of neural dysfunction in both types of diabetes. |
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The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetesAgedDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2FemaleGlucoseGlutamic AcidGlycated HemoglobinHumansMaleMiddle AgedNeurotransmitter AgentsProton Magnetic Resonance SpectroscopySynaptic Transmissiongamma-Aminobutyric AcidGlucose metabolism is pivotal for energy and neurotransmitter synthesis and homeostasis, particularly in Glutamate and GABA systems. In turn, the stringent control of inhibitory/excitatory tonus is known to be relevant in neuropsychiatric conditions. Glutamatergic neurotransmission dominates excitatory synaptic functions and is involved in plasticity and excitotoxicity. GABAergic neurochemistry underlies inhibition and predicts impaired psychophysical function in diabetes. It has also been associated with cognitive decline in people with diabetes. Still, the relation between metabolic homeostasis and neurotransmission remains elusive. Two 3T proton MR spectroscopy studies were independently conducted in the occipital cortex to provide insight into inhibitory/excitatory homeostasis (GABA/Glutamate) and to evaluate the impact of chronic metabolic control on the levels and regulation (as assessed by regression slopes) of the two main neurotransmitters of the CNS in type 2 diabetes (T2DM) and type 1 diabetes (T1DM). Compared to controls, participants with T2DM showed significantly lower Glutamate, and also GABA. Nevertheless, higher levels of GABA/Glx (Glutamate+Glutamine), and lower levels of Glutamate were associated with poor metabolic control in participants with T2DM. Importantly, the relationship between GABA/Glx and HbA1c found in T2DM supports a relationship between inhibitory/excitatory balance and metabolic control. Interestingly, this neurometabolic profile was undetected in T1DM. In this condition we found strong evidence for alterations in MRS surrogate measures of neuroinflammation (myo-Inositol), positively related to chronic metabolic control. Our results suggest a role for Glutamate as a global marker of T2DM and a sensitive marker of glycemic status. GABA/Glx may provide a signature of cortical metabolic state in poorly controlled patients as assessed by HbA1c levels, which indicate long-term blood Glucose control. These findings are consistent with an interplay between abnormal neurotransmission and metabolic control in particular in type 2 diabetes thereby revealing dissimilar contributions to the pathophysiology of neural dysfunction in both types of diabetes.Public Library of Science2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/106572http://hdl.handle.net/10316/106572https://doi.org/10.1371/journal.pone.0240907eng1932-6203d'Almeida, Otília C.Violante, Inês R.Quendera, BrunoMoreno, CarolinaGomes, LeonorCastelo-Branco, Miguelinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-06-14T08:43:31Zoai:estudogeral.uc.pt:10316/106572Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:00.598895Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes |
title |
The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes |
spellingShingle |
The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes d'Almeida, Otília C. Aged Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Female Glucose Glutamic Acid Glycated Hemoglobin Humans Male Middle Aged Neurotransmitter Agents Proton Magnetic Resonance Spectroscopy Synaptic Transmission gamma-Aminobutyric Acid |
title_short |
The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes |
title_full |
The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes |
title_fullStr |
The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes |
title_full_unstemmed |
The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes |
title_sort |
The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes |
author |
d'Almeida, Otília C. |
author_facet |
d'Almeida, Otília C. Violante, Inês R. Quendera, Bruno Moreno, Carolina Gomes, Leonor Castelo-Branco, Miguel |
author_role |
author |
author2 |
Violante, Inês R. Quendera, Bruno Moreno, Carolina Gomes, Leonor Castelo-Branco, Miguel |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
d'Almeida, Otília C. Violante, Inês R. Quendera, Bruno Moreno, Carolina Gomes, Leonor Castelo-Branco, Miguel |
dc.subject.por.fl_str_mv |
Aged Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Female Glucose Glutamic Acid Glycated Hemoglobin Humans Male Middle Aged Neurotransmitter Agents Proton Magnetic Resonance Spectroscopy Synaptic Transmission gamma-Aminobutyric Acid |
topic |
Aged Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Female Glucose Glutamic Acid Glycated Hemoglobin Humans Male Middle Aged Neurotransmitter Agents Proton Magnetic Resonance Spectroscopy Synaptic Transmission gamma-Aminobutyric Acid |
description |
Glucose metabolism is pivotal for energy and neurotransmitter synthesis and homeostasis, particularly in Glutamate and GABA systems. In turn, the stringent control of inhibitory/excitatory tonus is known to be relevant in neuropsychiatric conditions. Glutamatergic neurotransmission dominates excitatory synaptic functions and is involved in plasticity and excitotoxicity. GABAergic neurochemistry underlies inhibition and predicts impaired psychophysical function in diabetes. It has also been associated with cognitive decline in people with diabetes. Still, the relation between metabolic homeostasis and neurotransmission remains elusive. Two 3T proton MR spectroscopy studies were independently conducted in the occipital cortex to provide insight into inhibitory/excitatory homeostasis (GABA/Glutamate) and to evaluate the impact of chronic metabolic control on the levels and regulation (as assessed by regression slopes) of the two main neurotransmitters of the CNS in type 2 diabetes (T2DM) and type 1 diabetes (T1DM). Compared to controls, participants with T2DM showed significantly lower Glutamate, and also GABA. Nevertheless, higher levels of GABA/Glx (Glutamate+Glutamine), and lower levels of Glutamate were associated with poor metabolic control in participants with T2DM. Importantly, the relationship between GABA/Glx and HbA1c found in T2DM supports a relationship between inhibitory/excitatory balance and metabolic control. Interestingly, this neurometabolic profile was undetected in T1DM. In this condition we found strong evidence for alterations in MRS surrogate measures of neuroinflammation (myo-Inositol), positively related to chronic metabolic control. Our results suggest a role for Glutamate as a global marker of T2DM and a sensitive marker of glycemic status. GABA/Glx may provide a signature of cortical metabolic state in poorly controlled patients as assessed by HbA1c levels, which indicate long-term blood Glucose control. These findings are consistent with an interplay between abnormal neurotransmission and metabolic control in particular in type 2 diabetes thereby revealing dissimilar contributions to the pathophysiology of neural dysfunction in both types of diabetes. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/106572 http://hdl.handle.net/10316/106572 https://doi.org/10.1371/journal.pone.0240907 |
url |
http://hdl.handle.net/10316/106572 https://doi.org/10.1371/journal.pone.0240907 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1932-6203 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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