Slc2a8, also known as GLUT8, is a facilitative glucose transporter belonging to the SLC2A family. It is expressed in various tissues such as the testis, brain, liver, heart, uterus, ovary, and fat. It plays a crucial role in glucose and trehalose transport, which are involved in processes like autophagy, energy metabolism, and cellular respiration [1,3,4,5]. Genetic models, especially knockout mouse models, are valuable tools for studying its functions.

Slc2a8 -deficient mice show reproductive and growth impairments. Oocytes from these mice have abnormal metabolism and ATP production, and decidualization is impaired, leading to decreased litter size and smaller pups. These mice also have decreased body fat and are resistant to high-fat and carbohydrate diets [2]. In spermatozoa, Slc2a8 knockout reduces motility and mitochondrial potential, indicating its importance in sperm cell energy metabolism [5]. In human trophoblast cells, SLC2A8 RNA interference reduces glucose uptake, and its deficiency may impact placental glucose uptake and cellular respiration, potentially leading to placental insufficiency [4].

In conclusion, Slc2a8 is essential for reproductive processes, growth, and energy metabolism in various cell types. Studies using Slc2a8 -deficient mouse models have revealed its significance in diseases or conditions related to reproduction, growth, and metabolism, highlighting its potential as a therapeutic target in these areas.

References:

1. Rusmini, Paola, Cortese, Katia, Crippa, Valeria, Vaccari, Thomas, Poletti, Angelo. 2018. Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration. In Autophagy, 15, 631-651. doi:10.1080/15548627.2018.1535292. https://pubmed.ncbi.nlm.nih.gov/30335591/

2. Adastra, Katie L, Frolova, Antonina I, Chi, Maggie M, Carayannopoulos, Mary O, Moley, Kelle H. 2012. Slc2a8 deficiency in mice results in reproductive and growth impairments. In Biology of reproduction, 87, 49. doi:10.1095/biolreprod.111.097675. https://pubmed.ncbi.nlm.nih.gov/22649075/

3. Mayer, Allyson L, Higgins, Cassandra B, Heitmeier, Monique R, Hruz, Paul W, DeBosch, Brian J. 2016. SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose-induced autophagy. In Scientific reports, 6, 38586. doi:10.1038/srep38586. https://pubmed.ncbi.nlm.nih.gov/27922102/

4. Lipka, Aleksandra, Paukszto, Łukasz, Kennedy, Victoria C, Majewska, Marta, Anthony, Russell V. 2024. The Impact of SLC2A8 RNA Interference on Glucose Uptake and the Transcriptome of Human Trophoblast Cells. In Cells, 13, . doi:10.3390/cells13050391. https://pubmed.ncbi.nlm.nih.gov/38474355/

5. Gawlik, Verena, Schmidt, Stefan, Scheepers, Andrea, Joost, Hans-Georg, Schürmann, Annette. . Targeted disruption of Slc2a8 (GLUT8) reduces motility and mitochondrial potential of spermatozoa. In Molecular membrane biology, 25, 224-35. doi:10.1080/09687680701855405. https://pubmed.ncbi.nlm.nih.gov/18428038/