Disease relevance of SLC2A12

• GLUT-12 was identified in MCF-7 breast cancer cells by homology to the insulin-regulatable glucose transporter GLUT-4 [1].
• Targeting GLUT12 could provide novel methods for detection and treatment of breast and prostate cancer [2].
• Immunohistochemical staining of benign prostatic hyperplasia indicated expression of GLUT1 but not GLUT12 [3].
• Obesity, type-2 diabetes, training, conditions of de- and reinnervation (ALS) and regeneration (polymyositis) failed to induce GLUT8 or -12 expression [4].
• Ductal cell carcinoma in situ cells also stained strongly for GLUT12 [5].

High impact information on SLC2A12

• Some studies suggest a role for GLUT8 in the endoplasmic reticulum stress [6].
• The discovery of the brain expression of the translocable glucose transporters, GLUT4 then GLUT8, led to the question of their putative role in the central nervous system, particularly in relation to insulin effect [6].
• The glucose transporter GLUT8 cycles between intracellular vesicles and the plasma membrane [7].
• Endocytosis of the glucose transporter GLUT8 is mediated by interaction of a dileucine motif with the beta2-adaptin subunit of the AP-2 adaptor complex [7].
• As a consequence, GLUT8 accumulates at the plasma membrane at comparable levels to those observed in K44A-transfected cells [7].

Chemical compound and disease context of SLC2A12

• Estradiol and epidermal growth factor also increase GLUT12 protein levels in cultured breast cancer cells [2].

Biological context of SLC2A12

• The mouse GLUT-12 gene, located on chromosome 10, comprises at least five exons and encodes a 622 amino acid protein exhibiting 83% sequence identity and 91% sequence similarity to human GLUT-12 [8].
• Thus, our data demonstrate that recruitment of GLUT8 to the endocytic machinery occurs via direct interaction of the dileucine motif with beta2-adaptin, and that endocytosis might be the main site at which GLUT8 is likely to be regulated [7].
• Yeast two-hybrid analyses and GST pulldown assays reveal that the LL signal constitutes a binding site for the beta2-adaptin subunit of the heterotetrameric AP-2 adaptor complex, implicating this motif in targeting of GLUT8 to clathrin-coated vesicles [7].
• PURPOSE: The purpose of this study was to measure GLUT8 and GLUT12 mRNA levels in endurance-trained versus sedentary individuals in an effort to determine the effect of repeated days of contractile activity on gene expression [9].
• Primers were designed by using sequences that are not conserved in GLUT1 to GLUT5 and that contain the glycosylation region of GLUT8 [10].

Anatomical context of SLC2A12

• Immunoblotting demonstrated GLUT-12 expression in skeletal muscle, adipose tissue, and small intestine [1].
• Expression of the GLUT-12 gene was evident in all the major mouse adipose tissue depots (epididymal, perirenal, mesenteric, omental, and subcutaneous white; interscapular brown) [8].
• The GLUT-10 gene is also expressed in mouse adipose tissues and as with GLUT-12 expression occurred in the mature adipocytes as well as the stromal vascular cells [8].
• In human breast and prostate tumors and cultured cells, GLUT12 is located intracellularly and at the cell surface [2].
• We show that GLUT8 does not co-localize with GLUT4 and does not redistribute to the PM after treatment with insulin, ionophores or okadaic acid in these cell lines [11].

Associations of SLC2A12 with chemical compounds

• Identification of a novel glucose transporter-like protein-GLUT-12 [1].
• The apical localization of GLUT12 in the distal tubules and collecting ducts suggests that it could contribute to additional glucose reabsorption in the late nephron [12].
• Changing the glutamate to arginine as found in GLUT4 (RRXXXLL) alters GLUT8 endocytosis and retains the transporter at the PM [11].
• In the current study, we have utilized the Xenopus laevis oocyte expression system to assay transport of the glucose analog 2-deoxy-D-glucose and characterize the glucose transport properties and hexose affinities of GLUT12 [13].
• METHODS: Reverse transcription-polymerase chain reaction was performed on total RNA extracted from cultured prostate carcinoma cells LNCaP, C4, C4-2, and C4-2B using primers to amplify GLUT1, GLUT12, or the housekeeping gene, 36B4 [3].

Other interactions of SLC2A12

• Immunofluorescent studies demonstrated that GLUT4 and GLUT12 were predominantly expressed in type I oxidative fibers; however, GLUT5 was expressed predominantly in type II (white) fibers [14].
• Similarly, thirteen members of the family of facilitative sugar transporters (GLUT1-GLUT12 and HMIT; gene name SLC2A) are now recognised [15].
• Genomic organization of GLUT-12 is highly conserved with GLUT-10 but distinct from GLUTs 1-5 [1].
• GLUT6 and GLUT8 appear to be regulated by sub-cellular redistribution, because they are targeted to intra-cellular compartments by dileucine motifs in a dynamin dependent manner [16].
• The mRNA for three of these, the glucose transporters (GLUT) GLUT8, GLUT11 and GLUT12, have been detected in human skeletal muscle [4].

Analytical, diagnostic and therapeutic context of SLC2A12

• Immunofluorescence showed that, in the absence of insulin, GLUT-12 is localized to the perinuclear region in MCF-7 cells [1].
• An interspecies GLUT8 - sequence alignment revealed the presence of a highly conserved late endosomal/lysosomal-targeting motif ([DE]XXXL[LI]) [11].
• In further studies, paraffin sections of fetal membranes were analyzed by immunohistochemistry with GLUT12 and GLUT1-specific polyclonal antibodies [17].
• RT-PCR and Western blotting of extracts of amnion and choriodecidua from four normal term placentas identified GLUT12 mRNA and protein expression [17].
• Cultured cell monolayers were incubated with antibodies to GLUT1 or GLUT12 and a peripheral Golgi protein, Golgi 58K, for detection by immunofluorescent confocal microscopy [3].

References