One Molecule for Mental Nourishment and More: Glucose Transporter Type 1—Biology and Deficiency Syndrome
Glucose transporter type 1 (Glut1) is the main transporter involved in the cellular uptake of glucose into many tissues, and is highly expressed in the brain and in erythrocytes. Glut1 deficiency syndrome is caused mainly by mutations of the <i>SLC2A1</i> gene, impairing passive glucose...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/6/1249 |
| _version_ | 1827662229791571968 |
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| author | Romana Vulturar Adina Chiș Sebastian Pintilie Ilinca Maria Farcaș Alina Botezatu Cristian Cezar Login Adela-Viviana Sitar-Taut Olga Hilda Orasan Adina Stan Cecilia Lazea Camelia Al-Khzouz Monica Mager Mihaela Adela Vințan Simona Manole Laura Damian |
| author_facet | Romana Vulturar Adina Chiș Sebastian Pintilie Ilinca Maria Farcaș Alina Botezatu Cristian Cezar Login Adela-Viviana Sitar-Taut Olga Hilda Orasan Adina Stan Cecilia Lazea Camelia Al-Khzouz Monica Mager Mihaela Adela Vințan Simona Manole Laura Damian |
| author_sort | Romana Vulturar |
| collection | DOAJ |
| description | Glucose transporter type 1 (Glut1) is the main transporter involved in the cellular uptake of glucose into many tissues, and is highly expressed in the brain and in erythrocytes. Glut1 deficiency syndrome is caused mainly by mutations of the <i>SLC2A1</i> gene, impairing passive glucose transport across the blood–brain barrier. All age groups, from infants to adults, may be affected, with age-specific symptoms. In its classic form, the syndrome presents as an early-onset drug-resistant metabolic epileptic encephalopathy with a complex movement disorder and developmental delay. In later-onset forms, complex motor disorder predominates, with dystonia, ataxia, chorea or spasticity, often triggered by fasting. Diagnosis is confirmed by hypoglycorrhachia (below 45 mg/dL) with normal blood glucose, 18F-fluorodeoxyglucose positron emission tomography, and genetic analysis showing pathogenic <i>SLC2A1</i> variants. There are also ongoing positive studies on erythrocytes’ Glut1 surface expression using flow cytometry. The standard treatment still consists of ketogenic therapies supplying ketones as alternative brain fuel. Anaplerotic substances may provide alternative energy sources. Understanding the complex interactions of Glut1 with other tissues, its signaling function for brain angiogenesis and gliosis, and the complex regulation of glucose transportation, including compensatory mechanisms in different tissues, will hopefully advance therapy. Ongoing research for future interventions is focusing on small molecules to restore Glut1, metabolic stimulation, and <i>SLC2A1</i> transfer strategies. Newborn screening, early identification and treatment could minimize the neurodevelopmental disease consequences. Furthermore, understanding Glut1 relative deficiency or inhibition in inflammation, neurodegenerative disorders, and viral infections including COVID-19 and other settings could provide clues for future therapeutic approaches. |
| first_indexed | 2024-03-10T00:22:11Z |
| format | Article |
| id | doaj.art-cb97ee3d57a84e7cb61323360b93fe59 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:22:11Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-cb97ee3d57a84e7cb61323360b93fe592023-11-23T15:41:31ZengMDPI AGBiomedicines2227-90592022-05-01106124910.3390/biomedicines10061249One Molecule for Mental Nourishment and More: Glucose Transporter Type 1—Biology and Deficiency SyndromeRomana Vulturar0Adina Chiș1Sebastian Pintilie2Ilinca Maria Farcaș3Alina Botezatu4Cristian Cezar Login5Adela-Viviana Sitar-Taut6Olga Hilda Orasan7Adina Stan8Cecilia Lazea9Camelia Al-Khzouz10Monica Mager11Mihaela Adela Vințan12Simona Manole13Laura Damian14Department of Molecular Sciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaDepartment of Molecular Sciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaFaculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaChemistry Department, Oxford University, Oxford OX1 3TA, UKFaculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaDepartment of Physiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaInternal Medicine Department, 4th Medical Clinic, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaInternal Medicine Department, 4th Medical Clinic, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaDepartment of Neuroscience, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaDepartment Mother and Child, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaDepartment Mother and Child, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaDepartment of Neuroscience, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaDepartment of Neuroscience, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaDepartment of Radiology and Medical Imaging, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaDepartment of Rheumatology, Emergency Clinical County Hospital Cluj, Centre for Rare Autoimmune and Autoinflammatory Diseases (ERN-ReCONNET), 400347 Cluj-Napoca, RomaniaGlucose transporter type 1 (Glut1) is the main transporter involved in the cellular uptake of glucose into many tissues, and is highly expressed in the brain and in erythrocytes. Glut1 deficiency syndrome is caused mainly by mutations of the <i>SLC2A1</i> gene, impairing passive glucose transport across the blood–brain barrier. All age groups, from infants to adults, may be affected, with age-specific symptoms. In its classic form, the syndrome presents as an early-onset drug-resistant metabolic epileptic encephalopathy with a complex movement disorder and developmental delay. In later-onset forms, complex motor disorder predominates, with dystonia, ataxia, chorea or spasticity, often triggered by fasting. Diagnosis is confirmed by hypoglycorrhachia (below 45 mg/dL) with normal blood glucose, 18F-fluorodeoxyglucose positron emission tomography, and genetic analysis showing pathogenic <i>SLC2A1</i> variants. There are also ongoing positive studies on erythrocytes’ Glut1 surface expression using flow cytometry. The standard treatment still consists of ketogenic therapies supplying ketones as alternative brain fuel. Anaplerotic substances may provide alternative energy sources. Understanding the complex interactions of Glut1 with other tissues, its signaling function for brain angiogenesis and gliosis, and the complex regulation of glucose transportation, including compensatory mechanisms in different tissues, will hopefully advance therapy. Ongoing research for future interventions is focusing on small molecules to restore Glut1, metabolic stimulation, and <i>SLC2A1</i> transfer strategies. Newborn screening, early identification and treatment could minimize the neurodevelopmental disease consequences. Furthermore, understanding Glut1 relative deficiency or inhibition in inflammation, neurodegenerative disorders, and viral infections including COVID-19 and other settings could provide clues for future therapeutic approaches.https://www.mdpi.com/2227-9059/10/6/1249Glut1epilepsymovement disordersinborn errors of metabolismcognitive impairmentglucose uptake |
| spellingShingle | Romana Vulturar Adina Chiș Sebastian Pintilie Ilinca Maria Farcaș Alina Botezatu Cristian Cezar Login Adela-Viviana Sitar-Taut Olga Hilda Orasan Adina Stan Cecilia Lazea Camelia Al-Khzouz Monica Mager Mihaela Adela Vințan Simona Manole Laura Damian One Molecule for Mental Nourishment and More: Glucose Transporter Type 1—Biology and Deficiency Syndrome Biomedicines Glut1 epilepsy movement disorders inborn errors of metabolism cognitive impairment glucose uptake |
| title | One Molecule for Mental Nourishment and More: Glucose Transporter Type 1—Biology and Deficiency Syndrome |
| title_full | One Molecule for Mental Nourishment and More: Glucose Transporter Type 1—Biology and Deficiency Syndrome |
| title_fullStr | One Molecule for Mental Nourishment and More: Glucose Transporter Type 1—Biology and Deficiency Syndrome |
| title_full_unstemmed | One Molecule for Mental Nourishment and More: Glucose Transporter Type 1—Biology and Deficiency Syndrome |
| title_short | One Molecule for Mental Nourishment and More: Glucose Transporter Type 1—Biology and Deficiency Syndrome |
| title_sort | one molecule for mental nourishment and more glucose transporter type 1 biology and deficiency syndrome |
| topic | Glut1 epilepsy movement disorders inborn errors of metabolism cognitive impairment glucose uptake |
| url | https://www.mdpi.com/2227-9059/10/6/1249 |
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