Disease relevance of SLC2A2

• Of the 15 squamous cell lung carcinomas, 6 showed amplification for at least 1 of the genes, with BCHE and SLC2A2 as the genes most frequently amplified [1].
• Amplification of the genes BCHE and SLC2A2 in 40% of squamous cell carcinoma of the lung [1].
• Mutations of SLC2A2 were detected in historical FBS patients in whom some of the characteristic clinical features (hepatorenal glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy) and the effect of therapy were described for the first time [2].
• The characterization of the human GLUT2 gene will facilitate studies of its role in the development of diabetes mellitus [3].
• A mutation in GLUT2, not in phosphorylase kinase subunits, in hepato-renal glycogenosis with Fanconi syndrome and low phosphorylase kinase activity [4].

Psychiatry related information on SLC2A2

• Psychological stress impairs Na+-dependent glucose absorption and increases GLUT2 expression in the rat jejunal brush-border membrane [5].

High impact information on SLC2A2

• We summarize evidence supporting the idea that glucose metabolism is required for GSIS and that the GLUT-2 facilitated glucose transporter and the glucose phosphorylating enzyme glucokinase play important roles in measuring changes in extracellular glucose concentration [6].
• A 38% decrease in IB1 protein content resulted in a 49% and a 41% reduction in SLC2A2 and INS (encoding insulin) mRNA expression, respectively [7].
• Here we report mutations in the gene encoding the facilitative glucose transporter 2 (GLUT2) in three FBS families, including the original patient described in 1949 by Fanconi and Bickel [8].
• Glucose uptake into pancreatic beta cells by means of the glucose transporter GLUT-2, which has a high Michaelis constant, is essential for the normal insulin secretory response to hyperglycemia [9].
• Whenever fewer than 60% of beta cells were GLUT-2-positive, the response to glucose was absent and hyperglycemia exceeded 11 mM plasma glucose [10].

Chemical compound and disease context of SLC2A2

• To address these issues, we injected the liver of streptozotocin-induced diabetic rats with hemagglutinating virus of Japan-envelope (HVJ-E) vectors containing Epstein-Barr virus (EBV) plasmids encoding the genes for insulin and the GLUT 2 transporter [11].

Biological context of SLC2A2

• Together, our reverse chromosome painting data and our PCR analysis indicate gene amplification at 3q26 in 40% of all squamous cell lung carcinomas with BCHE and SLC2A2 as possible target genes of the amplification unit in squamous cell lung carcinoma [1].
• We conclude that the SNPs of SLC2A2 predict the conversion to diabetes in obese subjects with IGT [12].
• All four SNPs of SLC2A2 predicted the conversion to diabetes, and rs5393 (AA genotype) increased the risk of type 2 diabetes in the entire study population by threefold (odds ratio 3.04, 95% CI 1.34-6.88, P = 0.008) [12].
• No mutational hot spots within SLC2A2 or even within homologous sequences among the genes for facilitative glucose transporters were detected [2].
• Human beta-cells differ from rodent beta-cells in glucose transporter gene expression (predominantly GLUT1 instead of GLUT2), explaining their low Km (3 mmol/liter) and low VMAX (3 mmol/min per liter) for 3-O-methyl glucose transport [13].

Anatomical context of SLC2A2

• IL12A was amplified as single gene in three tumors and in a subline of the DU145 cell line, SLC2A2 in one tumor [14].
• The gene encoding the predominant facilitative glucose transporter expressed in pancreatic beta-cells and hepatocytes, termed GLUT2, has been cloned and characterized [3].
• Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter [15].
• The classical expression of GLUT1-5 in different normal human tissues was confirmed, however, we were unable to detect GLUT2 in human pancreatic islet cells [16].
• We have found GLUT-2 and glucokinase mRNAs in several brain regions, including the ventromedial and arcuate nuclei of the hypothalamus [17].

Associations of SLC2A2 with chemical compounds

• Polymorphisms in the SLC2A2 (GLUT2) gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study [12].
• The 100-fold lower GLUT2 abundance in human versus rat beta-cells is associated with a 10-fold slower uptake of alloxan, explaining their resistance to this rodent diabetogenic agent [13].
• The extensive expression of GLUT2 and 5 (glucose/fructose and fructose transporters, respectively) in malignant human tissues indicates that fructose may be a good energy substrate in tumor cells [16].
• Transport of low concentrations of fructose was not affected by 2-deoxy-D-glucose, a glucose analog that is transported by GLUT1 and GLUT2 [18].
• Thus, this mutation in GLUT2 is unlikely the cause of a low AIR in Pima Indians [19].
• Permanent apical GLUT2, resulting in increased sugar absorption, is a characteristic of experimental diabetes and of insulin-resistant states induced by fructose and fat [20].

Physical interactions of SLC2A2

• Moreover, D-glucose and maltose competitively inhibit fructose transport by GLUT2 and galactose transport by GLUT3, indicating that the transport of the alternative substrates for these transporters is likely to be mediated by the same outward-facing sugar-binding site used by glucose [21].

Regulatory relationships of SLC2A2

• We, therefore, investigated the potential role of PDX-1 in the transcriptional control of GLUT2 [22].
• [Val12] HRAS downregulates GLUT2 in beta cells of transgenic mice without affecting glucose homeostasis [23].
• To determine if the functional unit of the glucose transporter was a monomer or higher-order multimer, the high-affinity transporter GLUT3 was coexpressed with either the low-affinity GLUT2 or a GLUT3 mutant which contained a transport inactivating Trp410-->Leu substitution [24].
• Increased IgG binding could be removed by absorption with GLUT-2-expressing cells but not with GLUT-1-expressing cells [25].
• AdHNF6 infection alone caused a 2-fold increase in hepatic Glut-2 levels, suggesting that HNF 6 stimulates in vivo transcription of the Glut-2 gene [26].

Other interactions of SLC2A2

• The genes SI, BCHE, and SLC2A2 were amplified in both tumors; and (c) we analyzed 15 additional paraffin-embedded tissues to determine the amplification frequency of these genes [1].
• These data demonstrate that the murine GLUT2 promoter is controlled by the PDX-1 homeobox factor through the identified GLUT2TAAT motif [22].
• Increased glycaemia after meals may be recognized by specific hypothalamic neurones due to the high Km of GLUT-2 and glucokinase [17].
• This residue exists in the fifth membrane spanning domain, and Val at this position is conserved in mouse and rat GLUT 2, and human GLUT 1 to GLUT 4 [27].
• Variability of the pancreatic islet beta cell/liver (GLUT 2) glucose transporter gene in NIDDM patients [27].

Analytical, diagnostic and therapeutic context of SLC2A2

• Although the level of GLUT2 is frequently reduced in animal models of type II diabetes, GLUT2 does not limit glucose metabolism in beta cells and does not appear to regulate glucose induction of insulin secretion [28].
• Hexose uptake assays and immunoblotting experiments revealed that the breast carcinoma cell lines MCF-7 and MDA-468 express the glucose transporters GLUT1 and GLUT2, isoforms expressed in both normal and neoplastic breast tissue [29].
• Functional and biochemical studies were conducted by reporter assay using glucose-transporter type 2 (GLUT2) or insulin promoters and electrophoretic mobility shift assay, respectively [30].
• Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment [31].
• Gastric emptying, measured in awake rats, was significantly inhibited by perfusion of the intestine with glucose (60 and 90 mg); this effect was mimicked by alpha-methyl glucose (nonmetabolizable substrate of SGLT-1 and -3) but not 2-deoxy-d-glucose (substrate for GLUT-2) or isoosmotic mannitol [32].

References