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Glucose transporter class I (consisting of GLUT1, GLUT2, GLUT3, GLUT4, and GLUT14) (None for the class; individual family members are commonly abbreviated as GLUT1, GLUT2, GLUT3, GLUT4, and GLUT14)

Target
None for the class; individual family members are commonly abbreviated as GLUT1, GLUT2, GLUT3, GLUT4, and GLUT14
Molecular classification
Transporter, Facilitated diffusion protein, Major facilitator superfamily (MFS), Integral membrane protein
01

Overview

Glucose transporter class I refers to a group of membrane proteins that facilitate the passive transport of glucose (and sometimes other sugars such as galactose and mannose) across cellular membranes in response to concentration gradients. These proteins are encoded by SLC2 family genes and share a common molecular structure: 12 transmembrane domains and cytoplasmic amino and carboxyl termini. Each isoform has a distinct tissue distribution and regulates glucose uptake according to cellular needs; for example, GLUT1 is important for basal glucose uptake in almost all cells, especially in the brain and erythrocytes; GLUT4 is insulin-regulated and found in muscle and adipose tissue; GLUT2 is a low-affinity, high-capacity transporter in liver, pancreas, and kidney; GLUT3 is prevalent in neurons for high-affinity glucose uptake; GLUT14 is expressed in testes. Overexpression of several GLUT1-class transporters is a hallmark of cancer and other pathologies, making them targets for drug development and biomarker analysis.

Other names
Class I glucose transportersGLUT1/GLUT2/GLUT3/GLUT4/GLUT14 familySLC2A1/SLC2A2/SLC2A3/SLC2A4/SLC2A14 (gene names)
02

Mechanism of action

Inhibition of glucose transport activity Reduction of cellular glucose uptake leading to energy deprivation, especially in rapidly growing tumor cells

03

Biological functions

Glucose transport (facilitated diffusion)Cellular glucose uptakeEnergy homeostasisRegulation of metabolismBasal and insulin-stimulated glucose uptake
04

Disease associations

Cancer (GLUT1 and GLUT3 are often upregulated in tumors)Diabetes mellitus (GLUT4 dysfunction in insulin resistance)Neurological disorders (GLUT1 deficiency syndrome)Cardiovascular disease (GLUT1 in endothelial cells of barrier tissues)Other metabolic diseases
05

Safety considerations

Risk of hypoglycemia and impaired tissue function if glucose transport is inhibitedOff-target tissue effects (GLUTs are expressed in essential tissues, e.g., brain, heart, muscle, etc.)Potential neurological deficits (especially with GLUT1 inhibition)
06

Interacting drugs

Cytochalasin B (inhibitor)

4 more in the full profile.

07

Biomarkers

GLUT1 expression in tumor tissue (diagnostic/prognostic for cancer)GLUT4 translocation (assessed in studies of insulin sensitivity)Genetic testing for GLUT1 deficiency syndrome

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