Facilitative glucose transporters (GLUT) are proteins that mediate glucose transmembrane transport in the form of facilitated diffusion, which play an important role in regulating cell energy metabolism. There are many breakthroughs in researches of facilitative GLUT in recent years. It has been known that there are 14 subtypes of facilitative GLUT with obvious tissue specificity in distribution and physiological function. In the present review, the tissue and cellular distribution, subcellular localization, expression regulation, physiological function and the relationship to diseases of facilitative GLUT subtypes were summarized, in order to further understand their physiological and pathophysiological significances.
Biological Transport ; Disease ; Energy Metabolism ; Glucose ; Glucose Transport Proteins, Facilitative ; physiology ; Humans

BACKGROUND: Malignant cells exhibit increased glycolytic metabolism, and in many cases increased glucose transporter gene expression. The authors hypothesized that GLUT1 glucose transporter expression is increased in gallbladder carcinoma, and the degree of expression might have prognostic significance. METHODS: To evaluate a possible prognostic factor, we studied the expression of GLUT1 glucose transporter by an immunohistochemical method in 56 gallbladder carcinomas from patients and we compared these results with established prognostic factors. RESULTS: Of the 56 cases, 34 (60.7%) were positive for GLUT1. The expression of GLUT1 was not associated with patient age, sex and histologic type. Whereas the expression of GLUT1 was significantly correlated with depth of tumor invasion and lymph node and distant metastases. CONCLUSIONS: GLUT1 glucose transporter expression is strongly associated with poor prognostic factors of the gallbladder carcinoma and the assessment of the extent of GLUT1 immunostaining identifies patient with poorer prognosis.
Gallbladder* ; Gene Expression ; Glucose Transport Proteins, Facilitative* ; Glucose* ; Humans ; Lymph Nodes ; Metabolism ; Neoplasm Metastasis ; Prognosis

OBJECTIVETo study the expression level and significance of glucose transporter 1 (Glut-1) in normal breast tissue, adenosis, adenoma and breast carcinoma.

METHODSA total of 147 cases of female breast tissue samples, including 92 cases of invasive ductal carcinoma, 26 cases of breast fibroadenoma, 24 cases of breast adenosis and 5 cases of normal breast tissues, were collected for quantitative detection of the expression of Glut-1 protein by immunohistochemistry (EnVision method) and Western blot, and its mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTSIn normal breast tissue and benign lesions of the breast, Glut-1 was undetectable or only weakly detectable in cytoplasm of ductal and acinar epithelia. In contrast, the intensity of Glut-1 staining was significantly higher in invasive ductal carcinomas (P = 0.0002) with protein expression predominantly in cellular membrane and lesser in cytoplasm. Western blot and RT-PCR analyses showed that the expression of Glut-1 protein and mRNA were significantly increased in invasive ductal carcinoma than fibroadenoma (P =0.001 for protein; P <0.05 for mRNA) and adenosis (P =0.001 for protein; P < 0.05 for mRNA). There was a significant difference among groups (P = 0.0002 for protein; P = 0.0001 for mRNA).

CONCLUSIONSGlucose transport activity, as indicated by Glut-1 protein and its mRNA expression, significantly increases in breast carcinoma than non-cancerous lesions. The over-expression of Glut-1 in breast carcinoma is tightly coupled with tumor cell proliferation, invasion and metastasis, implying that Glut-1 may serve as a new marker in the early diagnosis and prognostication of breast malignancy as well as a new therapeutic target.

Breast Neoplasms ; metabolism ; Carcinoma, Ductal, Breast ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Glucose ; physiology ; Glucose Transport Proteins, Facilitative ; genetics ; metabolism ; Glucose Transporter Type 1 ; genetics ; metabolism ; Humans ; Prognosis

Fanconi-Bickel syndrome is a rare autosomal recessive disorder caused by a mutation in the facilitative glucose transporter 2 gene (GLUT2 or SLC2A2 gene) that codes for the glucose transporter protein 2 expressed in hepatocytes, pancreatic beta-cells, enterocytes, and renal tubular cells. Mutation of this gene leads to defective carbohydrate metabolism, hepatomegaly, glucose intolerance, proximal renal tubular dysfunction, and hypophosphatemic rickets. We report a case of Fanconi-Bickel syndrome in an 18-year-old man who presented due to renal glycosuria; a mutation was identified in the GLUT2 gene (c.482C > A + c.1556G > A). To the best of our knowledge, unlike previous reports of Fanconi-Bickel syndrome, this case was relatively unusual in that it caused only mild clinical signs.
Carbohydrate Metabolism ; Enterocytes ; Fanconi Syndrome ; Glucose Intolerance ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 2 ; Hepatocytes ; Hepatomegaly ; Hypophosphatemic Rickets, X-Linked Dominant

BACKGROUND/AIMS: Malignant cells exhibit increased glycolytic metabolism, and in many cases increased glucose transporter gene expression. We studied the expression of the glucose transporters in hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(CC). also, examined the usefulness of Glut-1 glucose transporter in the discrimination of HCC from CC. METHODS AND RESULTS: 23 HCC, 15 CC and 8 normal liver tissues were investigated immunohistochemically with Glut-1 glucose transporter. Immunostaning was regarded as positive when more than 5% of cells were stained. Among 38 liver tumor cases, Glut-1 was stained in 15(40%). in 2(9%) of 23 HCC and in 13(87%) of 15 CC were positive.(P=0.001) In HCC, underlying cirrhosis, 18(78%) were negative.(P=0.04) Other prognostic factors: histologic type, lymph node metastasis, distant metastasis did not show any significant correlation. CONCLUSION: Differential diagnosis between HCC and CC could be made by Glut-1 glucose transporter expression
Carcinoma, Hepatocellular* ; Cholangiocarcinoma* ; Diagnosis, Differential ; Discrimination (Psychology) ; Fibrosis ; Gene Expression ; Glucose Transport Proteins, Facilitative* ; Glucose* ; Liver ; Lymph Nodes ; Metabolism ; Neoplasm Metastasis

Fanconi-Bickel syndrome is a rare autosomal recessive disorder of the carbohydrate metabolism recently demonstrated to be caused by mutations in GLUT2, the gene for the glucose transporter protein 2 expressed in the liver, pancreatic beta islet-cells, intestine and kidney. Typical clinical and laboratory findings of Fanconi-Bickel syndrome are hepatomegaly secondary to glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic proximal tubular nephropathy and severe short stature. Several cases have been reported in other countries after Fanconi and Bickel in Switzerland first reported this syndrome in 1949. We experienced the first Korean case of Fanconi-Bickel syndrome in a neonate presented with hyperglycemia and hypergalactosemia that was initially diagnosed as transient neonatal diabetes mellitus and galactosemia. We also identified a novel mutation(K5X) in the GLUT2 gene.
Carbohydrate Metabolism ; Diabetes Mellitus* ; Fanconi Syndrome* ; Galactose ; Galactosemias* ; Glucose ; Glucose Transport Proteins, Facilitative ; Glycogen ; Hepatomegaly ; Humans ; Hyperglycemia ; Hypoglycemia ; Infant, Newborn ; Intestines ; Kidney ; Liver ; Switzerland

BACKGROUND: Previous studies have shown that 17beta-estradiol activates AMP-activated protein kinase (AMPK) in rodent muscle and C2C12 myotubes and that acute 17beta-estradiol treatment rapidly increases AMPK phosphorylation possibly through non-genomic effects but does not stimulate glucose uptake. Here, we investigated whether 24-hour 17beta-estradiol treatment stimulated glucose uptake and regulated the expression of genes associated with glucose and energy metabolism through the genomic effects of estrogen receptor (ER) in C2C12 myotubes. METHODS: C2C12 myotubes were treated with 17beta-estradiol for 24 hours, and activation of AMPK, uptake of glucose, and expression of genes encoding peroxisome proliferator-activated receptor γ coactivator 1α, carnitine palmitoyltransferase 1β, uncoupling protein 2, and glucose transporter 4 were examined. Furthermore, we investigated whether AMPK inhibitor (compound C) or estrogen receptor antagonist (ICI182.780) treatment reversed 17beta-estradiol-induced changes. RESULTS: We found that 24-hour treatment of C2C12 myotubes with 17beta-estradiol stimulated AMPK activation and glucose uptake and regulated the expression of genes associated with glucose and energy metabolism. Treatment of C2C12 myotubes with the estrogen receptor antagonist (ICI182.780) reversed 17beta-estradiol-induced AMPK activation, glucose uptake, and changes in the expression of target genes. Furthermore, treatment with the AMPK inhibitor (compound C) reversed 17beta-estradiol-induced glucose uptake and changes in the expression of target genes. CONCLUSION: Our results suggest that 17beta-estradiol stimulates AMPK activation and glucose uptake and regulates the expression of genes associated with glucose and energy metabolism in C2C12 myotubes through the genomic effects of ER.
AMP-Activated Protein Kinases ; Carnitine O-Palmitoyltransferase ; Energy Metabolism ; Estrogens ; Glucose Transport Proteins, Facilitative ; Glucose ; Muscle Fibers, Skeletal ; Peroxisomes ; Phosphorylation ; Rodentia

PURPOSE: To characterize the relationship between serum estradiol levels and the expression of glucose transporter type 4 (Glut4) in the pubococcygeus and iliococcygeus muscles in female rats. METHODS: The muscles were excised from virgin rats during the metestrus and proestrus stages of the estrous cycle, and from sham and ovariectomized rats implanted with empty or estradiol benzoate–filled capsules. The expression of estrogen receptors (ERs) was inspected in the muscles at metestrus and proestrus. Relative Glut4 expression, glycogen content, and serum glucose levels were measured. Appropriate statistical tests were done to identify significant differences (P≤0.05). RESULTS: The pubococcygeus and iliococcygeus muscles expressed ERα and ERβ. Glut4 expression and glycogen content in the pubococcygeus muscle were higher at proestrus than at metestrus. No significant changes were observed in the iliococcygeus muscle. In ovariectomized rats, the administration of estradiol benzoate increased Glut4 expression and glycogen content in the pubococcygeus muscle alone. CONCLUSIONS: High serum estradiol levels increased Glut4 expression and glycogen content in the pubococcygeus muscle, but not in the iliococcygeus muscle.
Animals ; Benzoates ; Blood Glucose ; Capsules ; Estradiol* ; Estrous Cycle ; Female ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 4* ; Glucose* ; Glycogen ; Humans ; Metabolism ; Metestrus ; Muscles* ; Ovariectomy ; Pelvic Floor* ; Proestrus ; Rats* ; Receptors, Estrogen

Previous studies have shown that ginsenoside Rb1 (Rb1), one of active components in ginseng, can activate insulin signaling pathway and promote translocation of glucose transporters (GLUTs) to increase glucose uptake in adipocytes. However, the effect of Rb1 on the expressions of GLUTs remains unknown. In this study, the effects of Rb1 on GLUT1 and GLUT4 were observed in 3T3-L1 adipocytes and epididymal adipose tissue of db/db obese diabetic mice. Male db/db mice were treated with Rb1 by intraperitoneal injection at the dosage of 20 mg x kg(-1) for 14 d. Rb1 reduced HOMA-IR significantly (P < 0.05, n = 5), and FBG and FINS sowed declining trend after treatment with Rb1. Rb1 recovered the expressions of GLUT1 and GLUT4 and phosphorylation of AKT in adipose tissue of db/db mice. In vitro, glucose consumption in 3T3-L1 adipocytes treated with 10 micromol x L(-1) Rb1 for 24 h was elevated (P < 0.05, n=3), and mRNA of GLUT1 and GLUT4 were up-regulated (P < 0.05, n=3) and proteins of GLUT1 and GLUT4 were also increased. AKT was activated in adipocytes treated with Rb1 for 3 h. It can be concluded that ginsenoside Rb1 can up-regulate the expression of GLUTs in adipose tissue, in addition to activate insulin signalling pathway, which may partially account for its insulin sensitizing activity and regulating effect of glucose metabolism.
3T3 Cells ; Adipocytes ; drug effects ; Animals ; Cell Line ; Diabetes Mellitus, Experimental ; metabolism ; Ginsenosides ; pharmacology ; Glucose ; metabolism ; Glucose Transport Proteins, Facilitative ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Up-Regulation ; drug effects

BACKGROUND/OBJECTIVES: Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS: The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS: Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2- fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic beta-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS: Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic beta-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice.
Adiponectin ; AMP-Activated Protein Kinases ; Animals ; Anthocyanins ; Blood Glucose ; Body Weight ; C-Peptide ; Diabetes Complications ; Fasting ; Fibrosis ; Glucose Transport Proteins, Facilitative ; Glucose-6-Phosphatase ; Glycolysis ; Inflammation ; Insulin ; Insulin Resistance ; Islets of Langerhans ; Liver ; Metabolism ; Mice* ; Muscle, Skeletal ; Phosphoenolpyruvate ; Phosphorylation ; Zea mays*