Disease relevance of Slc2a8

• These data demonstrate that the lack of syntaxin 4 expression results in abnormal movement of GLUT8 in response to insulin, decreased insulin-stimulated glucose uptake, and increased apoptosis [1].
• To evaluate its presence at the plasma membrane, we generated a recombinant adenovirus for the expression of GLUT8 containing an extracellular myc epitope [2].
• We examined the subcellular distribution of a novel glucose transporter isoform (GLUT8) in murine N2A neuroblastoma cells [3].

High impact information on Slc2a8

• GLUT8 is a glucose transporter responsible for insulin-stimulated glucose uptake in the blastocyst [4].
• GLUT8 is a glucose transporter isoform expressed at high levels in testis; at intermediate levels in the brain, including the hippocampus; and at lower levels in the heart and several other tissues [5].
• We showed that expression of GLUT8 was not required for normal embryonic development and that glut8-/- mice had normal postnatal development, glucose homeostasis, and response to mild stress [5].
• GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis and heart function [5].
• 5. In parallel, 22% of the blastocysts from Stx4a+/- matings had no significant insulin-stimulated translocation of GLUT8 whereas 77% displayed either partial or complete translocation to the apical plasma membrane [1].

Biological context of Slc2a8

• Any decrease in GLUT8 cell surface expression results in increased apoptosis and pregnancy loss [1].
• GLUT8 is a novel glucose transporter protein that is widely distributed in tissues including liver, a central organ of regulation of glucose homeostasis [6].
• Because glucose transporters in the kidney play an important role in the local maintenance of intracellular glucose and plasma glucose homeostasis, the tissue distribution and regulation of glucose transporter GLUT8, a new member of the glucose transporter family with important functions in cellular survival, were examined [7].
• While up-regulation of GLUT8 protein occurred in both models of diabetes, only in streptozotocin diabetic livers was GLUT8 zonation altered [6].
• Additionally, GLUT8 expression was studied using two different models of insulin resistance, GLUT4-/- and db/db mice [7].

Anatomical context of Slc2a8

• Similar to GLUT4, GLUT8 translocates to the plasma membrane to increase glucose uptake at a stage in development when glucose serves as the main substrate [1].
• Thus, syntaxin 4 functions as the necessary t-SNARE protein responsible for correct fusion of the GLUT8-containing vesicle with the plasma membrane in the mouse blastocyst [1].
• Immunofluorescence microscopy of liver from wild-type mice demonstrated the highest levels of GLUT8 protein in perivenous hepatocytes pointing to its role in regulation of glycolytic flux [6].
• GLUT8 was localized to glomerular podocytes and tubular epithelial cells in the distal portion of the nephron [7].
• We showed that when expressed in PC12 cells, GLUT8 was located in a perinuclear compartment in which it showed partial colocalization with markers for the endoplasmic reticulum but not with markers for the trans-Golgi network, early endosomes, lysosomes, and synaptic-like vesicles [2].

Associations of Slc2a8 with chemical compounds

• By employing stable transfectants that expressed GLUT8-GFP, the effect of insulin and insulin-like growth factor-I, potassium chloride (depolarized state), and 3% oxygen on translocation of GLUT8 to the plasma membrane of N2A cells was examined immunohistochemically and by subfractionation, followed by Western blot analysis [3].
• However, when the internalization dileucine motif (L(12,13)) of GLUT8 was mutated to a dialanine motif (A(12,13)), GLUT8 colocalized with GLUT3 in the plasma membrane [3].

Regulatory relationships of Slc2a8

• Exposure to insulin in the embryos exposed to IGF-1R sense induced translocation of GLUT8 from intracellular compartments to the plasma membrane [8].

Other interactions of Slc2a8

• This difference in GLUT8 translocation directly correlated with one-third of blastocysts from Stx4a+/- mating having reduced rates of insulin-stimulated glucose uptake and 67% with wild-type rates [1].
• GLUT8 is a novel IGF-I/insulin-regulated glucose transporter expressed in the mouse blastocyst [1].
• Blastocysts exposed to IGF-1R antisense, however, failed to demonstrate any change in the intracellular location of GLUT8 with insulin treatment [8].
• Exogenous expression of GLUT8-green fluorescent protein (GFP) DNA constructs mimicked the endogenous GLUT8 localization to intracellular vesicles and minimally to the Giantin-positive Golgi [3].

Analytical, diagnostic and therapeutic context of Slc2a8

• Employing Western blot analysis and specific antibodies, GLUT4 and GLUT8 peaked during the suckling phase [9].
• In this study, we analyzed the GLUT8 expression in mouse testis during spermatogenesis by RT-PCR, Western blot and immunohistochemistry methods [10].

References