Molecular Structure, Biochemical Functions, Genetics, and Emerging Clinical Relevance of Glucose Transporters

In the human body, glucose acts as a major energy-producing fuel and regulator of energy homeostasis, enzyme functions, and gene transcription. The selective permeability of the lipid bilayer structure of the cell membrane makes it mandatory for glucose to require transport proteins for its transit into the cells. These include solute carrier integral membrane proteins such as glucose transporters (GLUTs) and sodium-glucose transporters. GLUTs belong to the major facilitator superfamily with a 12 transmembrane spanner topology, with GLUT1-13 sharing the same transmembrane sequence but variable transmembrane loops and terminal cytoplasmic ends of carbon and nitrogen. Phylogenetic analysis classifies GLUTs into three classes, with each class showing an affinity for a specific substrate. The tightly coupled relationship between glucose homeostasis and the nearly ubiquitous GLUTs has led to the investigation of their diverse roles in embryonic development, adult physiology, and clinical disorders including but not limited to inborn errors, diabetes mellitus, metabolic syndrome, and cancers. The current review is pivoted around the studies focusing on the structure and functions of members of the GLUT family, their chromosomal and organ-specific distribution, as well as the current evidence of their clinical implications and prospective therapeutic roles, specifically in cancers and metabolic disorders. The literature for the present work was retrieved from databases including Google Scholar, Web of Science, and PubMed.