3.3. Class III GLUTs
Class III contains GLUTs 6, 8, 10, 12 and HMIT/GLUT13. According to NCBI, slc2a6 has alias GLUT6 and GLUT9 proteins in humans, mice and X. tropicalis. GLUT6 is a hexose transporter protein. Mammalian GLUT6 is highly expressed in the brain, spleen and leukocytes [63]. One study linked an upregulation of GLUT6 to endometrial cancer in women [64]. Based on the NCBI Gene Database [32,37], GLUT6/SLC2A6 orthologs are present in 169 organisms including chicken, dog, cow, mouse, chimpanzee, Rhesus monkey, zebrafish, fruit fly, mosquito, X. tropicalis and X. laevis.
Based on sequence similarity, GLUT8 has been identified as an insulin-regulated glucose transporter. According to NCBI, GLUT8 binds cytochalasin β in a glucose-inhibitable manner. Mammalian GLUT8 may be dual-specific and is inhibitable by fructose. A recent study on the mouse atria suggests that GLUT8 has a role in glucose uptake in the mammalian heart, along with GLUT4 [65]. glut8/slc2a8 orthologs are conserved across 171 organisms including chicken, dog, mouse, rat, cow, chimpanzee, Rhesus monkey, X. tropicalis, zebrafish, fruit fly, A. thaliana and rice, according to NCBI. Similar to mammals, chicken GLUT8 is a known insulin-responsive glucose transporter with ubiquitous expression in cells and higher mRNA concentrations in adipose tissue and kidney [1].
According to the NCBI Gene Database, GLUT10 plays a role in glucose homeostasis regulation. Human GLUT10 has highest mRNA expression in the liver and pancreas [66]. In humans, genetic mutations of glut10/slc2a10 are associated with arterial tortuosity syndrome, a rare connective tissue disorder [67]. Based on NCBI, glut10/slc2a10 orthologs are conserved across 166 organisms including chicken, dog, mouse, rat, chimpanzee, Rhesus monkey, cow, X. tropicalis, X. laevis and zebrafish [32,37].
According to the Gene Database at NCBI, the slc2a12 encoded protein contains alias GLUT8 and GLUT12 in humans. GLUT12 can facilitate transport of a variety of hexoses [68]. Human GLUT12 is expressed in skeletal muscle, heart and prostate, with lower mRNA expression in the brain, placenta and kidneys [69]. A recent study implicated GLUT12 expression in the frontal cortex for its role in Alzheimer’s disease, a metabolic disease which impairs the brain’s ability to utilize glucose [70]. The GLUT12 level, as well as GLUT1 level, was shown to be elevated in hypertension and diabetic neuropathy in animal studies [71]. A recent study of GLUT12 in chicken skeletal and cardiac muscle suggests that GLUT12 may act as an insulin-sensitive transporter similar to GLUT4 in mammalian species [72]. Orthologs of glut12/slc2a12 are conserved across 177 organisms including chicken, dog, mouse, rat, chimpanzee, Rhesus monkey, cow, X. tropicalis, X. laevis, zebrafish, A. thaliana and rice, based on the NCBI Gene Database [32,37].
Studies on Xenopus oocytes have helped identify GLUT13 as a proton (H+) myo-inositol cotransporter with specificity for the transport of myo-inositol, inositol triphosphate and related stereoisomers [73,74]. Mammalian HMIT/GLUT13 is predominantly expressed in glial cells and some neurons and may be responsible for myo-inositol brain metabolism regulation [73]. Intracellular function of HMIT may also be responsible for mood control [74]. Genetic alterations of HMIT may also be associated with non-small-cell lung cancer [75] and Parkinson’s disease [76]. According to the NCBI Gene Database [32,37], glut13/slc2a13 orthologs are conserved across 151 organisms including chicken, dog, cow, chimpanzee, Rhesus monkey, mouse, rat, X. tropicalis, X. laevis, zebrafish, C. elegans, S. cerevisiae, K. lactis, E. gossypii, Schizosaccharomyces pombe (fission yeast), A. thaliana and rice.