One Molecule for Mental Nourishment and More: Glucose Transporter Type 1—Biology and Deficiency Syndrome

Abstract

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 SLC2A1 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 SLC2A1 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 SLC2A1 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.

Bridging the gap: glucose transporters, Alzheimer’s, and future therapeutic prospects

“…Because of its characteristics, GLUT1 is mainly accountable for constitutive glucose absorption. It can be found in almost all fetal tissues, as well as many adult tissues, and is abundant in endothelial cells of blood-tissue barriers in several organs, having the highest levels of expression in proliferating cell plasma membranes throughout embryonic development ( Veys et al, 2020 ; Vulturar et al, 2022 ). It is also found at high levels in the brain, skeletal muscle, and myocardium.…”

Development of Dementia in Type 2 Diabetes Patients: Mechanisms of Insulin Resistance and Antidiabetic Drug Development

“…T2DM increases the risk of cognitive impairment and IR is linked to a more rapid reduction in the memory-encoding mechanism and thinking skills [ 31 ]. Various types of genes, including SLC2A1–SLC2A14 and molecules (GLUT1–GLUT14), are actively involved in the transport of glucose in various regions of the brain and each cell type expresses multiple proteins [ 32 ]. GLUT proteins are classified into three classes.…”