Insulin stimulates glucose transport in muscle and fat cells by promoting the translocation of glucose transporter (GLUT4) to the cell surface. Phosphatidylinositide 3-kinase (PI3-kinase) has been implicated in this process. However, the involvement of protein kinase B (PKB)/Akt and PKC- zeta, those are known as the downstream target of PI3-kinase in regulation of GLUT4 translocation, is not known yet. An interesting possibility is that these protein kinases phosphorylate GLUT4 directly in this process. In the present study, PKB- alpha and PKC- zeta were added exogenously to GLUT4-containing vesicles purified from low density microsome (LDM) of the rat adipocytes by immunoadsorption and immunoprecipitation for direct phosphorylation of GLUT4. Interestingly GLUT4 was phosphorylated by PKC- zeta and its phosphorylation was increased in insulin stimulated state but GLUT4 was not phosphorylated by PKB- alpha. However, the GST-fusion proteins, GLUT4 C-terminal cytoplasmic domain (GLUT4C) and the entire major GLUT4 cytoplasmic domain corresponding to N-terminus, central loop and C-terminus in tandem (GLUT4NLC) were phosphorylated by both PKB- alpha and PKC- zeta. The immunoblots of PKC- zeta and PKB- alpha antibodies with GLUT4-containing vesicles preparation showed that PKC- zeta was co-localized with the vesicles but not PKB- alpha. From the above results, it is clear that PKC- zeta interacts with GLUT4-containing vesicles and it phosphorylates GLUT4 protein directly but PKB- alpha does not interact with GLUT4, suggesting that insulin-elicited signals that pass through PI3-kinase subsequently diverge into two independent pathways, an Akt pathway and a PKC- zeta pathway, and that later pathway contributes, at least in part, insulin stimulation of GLUT4 translocation in adipocytes via a direct GLUT4 phosphorylation.
Adipocytes* ; Animals ; Antibodies ; Cytoplasm ; Glucose ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 4 ; Immunoprecipitation ; Insulin ; Microsomes ; Phosphatidylinositol 3-Kinases ; Phosphorylation* ; Protein Kinases ; Proto-Oncogene Proteins c-akt ; Rats*

D-glucose is an essential fuel for metabolism in mammalian cells and the predominant fuel source for the brain. Transport of glucose across tissue barriers is mediated by stereospecific transporter proteins. Glut-1 is a major glucose transporter expressed on vascular endothelial cells comprising the blood brain barrier and is responsible for glucose entry into the brain. Impaired glucose transport across the blood brain barrier results in Glut-1 deficiency syndrome(DS). It is caused by haploinsufficiency of the blood brain barrier hexose carrier. Heterozygous mutations or hemizygosity of the GLUT-1 gene cause Glut-1 DS. It is characterized by infantile seizures refractory to anticonvulsants, developmental delay, acquired microcephaly, spasticity, ataxia, opsoclonus and other paroxysmal neurological phenomena, often occurring prior to meals. The diagnosis of Glut-1 DS is established in neurologically impaired patients with reduced cerebrospinal glucose concentration(hypoglycorrhachia) and lactate concentration in the absence of hypoglycemia. Decreased 3-O-methyl-D-glucose uptake in erythrocytes also supports the diagnosis of Glut-1 DS. Several treatment strategies have been pursued, none optimal, as it relates to the developmental encephalopahty associated with this clinical syndrome. Ketogenic diet has been effective in controlling seizures but has had little measurable effects on the associated cognitive impairments and behavioral disturbance. Current treatment is inadequate, and future studies should be directed at the mechanisms designed to upreglulate GLUT-1 expression, thereby increasing residual Glut-1 activity to 75 to 100%.
3-O-Methylglucose ; Anticonvulsants ; Ataxia ; Blood-Brain Barrier ; Brain ; Diagnosis ; Endothelial Cells ; Epilepsy ; Erythrocytes ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 1* ; Glucose* ; Haploinsufficiency ; Humans ; Hypoglycemia ; Ketogenic Diet ; Lactic Acid ; Meals ; Metabolism ; Microcephaly ; Muscle Spasticity ; Ocular Motility Disorders ; Seizures

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is caused by impaired glucose transport across the blood-brain barrier (BBB) and characterized by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and a low cerebrospinal glucose concentration (hypoglycorrhachia). A diagnosis of GLUT1-DS is biochemically established in neurologically impaired patients with hypoglycorrhachia in the normoglycemia. GLUT1-DS can be confirmed by mutation analysis of the solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) gene or reduced 3-O-methyl-D-glucose uptake into erythrocytes. The patient was a 12-year-old boy born at term. He had experienced seizures from 4 months of age. Electroencephalography (EEG) did not show epileptiform activity. Brain magnetic resonance imaging (MRI) revealed mild diffuse cortical atrophy and ventricular dilatation. Furthermore, he showed developmental delay, mental retardation, and ataxia, which all became more apparent with age progression. For 7 years, he had experienced paroxysmal episodes of atonic behavioral changes that were aggravated before meals or when he became tired. When he was 12 years old, cerebrospinal fluid (CSF) analysis revealed a low glucose concentration in the normal serum glucose and lactate levels. Under the impression of GLUT1-DS, mutation analysis of the SLC2A1 gene by direct sequencing was performed using white blood cells, and c.680-2delA of intron 5 was found. We describe a GLUT1-DS patient with a typical natural history of GLUT1-DS through a long term follow-up visits, with a novel splice site mutation (SLC2A1: c.6802delA).
3-O-Methylglucose ; Ataxia ; Atrophy ; Blood Glucose ; Blood-Brain Barrier ; Brain ; Cerebrospinal Fluid ; Child ; Diagnosis ; Dilatation ; Electroencephalography ; Erythrocytes ; Follow-Up Studies ; Glucose ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 1 ; Humans ; Intellectual Disability ; Introns ; Lactic Acid ; Leukocytes ; Magnetic Resonance Imaging ; Male ; Meals ; Microcephaly ; Muscle Spasticity ; Natural History ; Seizures

BACKGROUND: The diagnosis of atypical mucosal lesions by performing hematoxylin-eosin staining is too subjective, and it is also subject to considerable inter-observer variation. There is a need for reliable immunohistochemical markers that can give reproducible results and that are not subject to individual interpretation. METHODS: We reviewed a total of 199 cases of gastric biopsy specimens, which were all diagnosed as atypical mucosal lesions, and 124 cases of the adenocarcinomas specimens had been classified from category 1 (C1) to C5 according to the Vienna classification. We also examined the immunohistochemical expressions of the glucose transporter GLUT1 and the p53 protein in the gastric biopsy specimens to determine if they were useful markers for differentiatial diagnosis under the Vienna classifications. RESULTS: None of the specimens in categories C1 to C3 showed GLUT1 expression, but 10.1% of the C4 specimens and 25.0% of the C5 specimens were GLUT1-positive (p<0.05). The expression of p53 was undetectable in the C1 specimens, but this was expressed in 2.9% of the C2 specimens, 15.6% of the C3 specimens, 37.8% of the C4 specimens, and 65.3% of the C5 specimens (p<0.05). CONCLUSIONS: The Vienna classification is very applicable to the gastric biopsy specimens of the atypical mucosal lesions, and the GLUT1 and p53 expressions are candidates as highly useful markers to differentiate the Vienna C4 lesions from the C3 and C5 lesions.
Adenocarcinoma ; Biopsy* ; Classification ; Diagnosis ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 1 ; Observer Variation ; Stomach ; Tumor Suppressor Protein p53

BACKGROUND: Increased glucose uptake, a process that is mediated by glucose transporter (Glut1) proteins, is an important metabolic feature in a variety of cancer cells. The overexpression of Glut1 in human cancers is known to be related to a variety of histopathological parameters, including histological grade, proliferation rate, and lymphatic invasion. The principal objective of this study was to evaluate Glut1 expression in the spectrum of pulmonary neuroendocrine (NE) tumors including typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), and to characterize the relationship between Glut1 expression and the histologic grade of NE tumors. METHODS: 19 TC, 7 AC, 13 LCNEC, and 6 SCC patients were included in this study. The percentages of Glut1-positive tumor cells in these patients were determined. For statistical analysis, Glut1 expression was subdivided into a Glut1-low expression group (0-30%) and a Glut1-high expression group (31-90%). RESULTS: In our subgroup analyses, the histological grade of pulmonary neuroendocrine (NE) tumors was significantly correlated with Glut1 expression; TC (n=19, 3.6+/-4.2%), AC (n=7, 20.0+/-4.9%), LCNEC (n=13, 60.0+/-21.1%), and SCC (n=6, 74.2+/-16.9%). Glut1-high expression was significantly associated with high-grade NE tumors such as LCNEC and SCC (n=19, 62.6+/-21.0%) (p=0.000). CONCLUSIONS: The results of this study appear to indicate that Glut1 overexpression is a consistent feature of high-grade NE lung tumors.
Carcinoid Tumor ; Carcinoma, Neuroendocrine ; Carcinoma, Small Cell ; Glucose ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 1 ; Humans ; Immunohistochemistry ; Lung ; Lung Neoplasms ; Neuroendocrine Tumors ; Proteins

Lung cancer constitutes non-small cell lung cancer and small cell lung cancer. Positron emission tomography (PET) using F-18 labelled fluoro-deoxy glucose (FDG) has been evolving from a promising diagnostic tool in selective patients to an essential routine procedure in almost all lung cancer patients. Glucose transporter type 1 (Glut-1) plays a major role in determining FDG uptake in lung cancer, and immunoreactivity of Glut-1 reveala a high correlation with standardized uptake value (SUV) of FDG in primary tumor and metastatic lymph nodes of lung cancer. This review article aims to onsolidate the understanding of the role of FDG-PET in the management of lung cancer
Carcinoma, Non-Small-Cell Lung ; Glucose ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 1 ; Humans ; Lung Neoplasms* ; Lung* ; Lymph Nodes ; Positron-Emission Tomography ; Small Cell Lung Carcinoma

PURPOSE: Breast cancer of malignant tumor occurring in domestic women is a tumor frequently seen in the third order following uterine cervical cancer and gastric cancer. This tumor may be recur even following positive treatment, so various methods have been studied to elucidate risk factors for recurrence. In particular, among the various oncogenes concerned in the recurrence of breast cancer, some have been seen as prognostic factors. In a recent study of protein expression in the tumor cell, it was demonstrated that expression increases glucose uptake and utilization, and that Glut1 facilitating the glucose transporter is increased in expression in various tumors of body. Many studies have been conducted on the role of protein in this glucose transporter in breast cancer, yet more studies are required. METHODS: Dye studies were carried out according to an ordinary ABC method utilizing polyclonal anti-Glut1 antibody to detect Glut1 protein in 79 breast cancer samples. RESULTS: Among the 79 breast cancer tissue samples, 41 samples (52%) demonstrated expression of Glut1. Upon close examnination, the expression frequency of Glut1 in brest cancer in relation to existing breast cancer prognosis- related factors, showed a statistically significant correlation with the histologic grade of the breast cancer. CONCLUSION: As Glut1 positive expression was seen in the breast cancer cell, it is suggested that Glut1 is involved in the occurrence of breast cancer. In particular, in poorly differentiated breast cancer, the expression was frequency increased, which suggested its potential as a prognostic factor for breast cancer.
Breast Neoplasms* ; Breast* ; Female ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 1* ; Glucose* ; Humans ; Oncogenes ; Recurrence ; Risk Factors ; Stomach Neoplasms ; Uterine Cervical Neoplasms

PURPOSE: Breast cancer of malignant tumor occurring in domestic women is a tumor frequently seen in the third order following uterine cervical cancer and gastric cancer. This tumor may be recur even following positive treatment, so various methods have been studied to elucidate risk factors for recurrence. In particular, among the various oncogenes concerned in the recurrence of breast cancer, some have been seen as prognostic factors. In a recent study of protein expression in the tumor cell, it was demonstrated that expression increases glucose uptake and utilization, and that Glut1 facilitating the glucose transporter is increased in expression in various tumors of body. Many studies have been conducted on the role of protein in this glucose transporter in breast cancer, yet more studies are required. METHODS: Dye studies were carried out according to an ordinary ABC method utilizing polyclonal anti-Glut1 antibody to detect Glut1 protein in 79 breast cancer samples. RESULTS: Among the 79 breast cancer tissue samples, 41 samples (52%) demonstrated expression of Glut1. Upon close examnination, the expression frequency of Glut1 in brest cancer in relation to existing breast cancer prognosis- related factors, showed a statistically significant correlation with the histologic grade of the breast cancer. CONCLUSION: As Glut1 positive expression was seen in the breast cancer cell, it is suggested that Glut1 is involved in the occurrence of breast cancer. In particular, in poorly differentiated breast cancer, the expression was frequency increased, which suggested its potential as a prognostic factor for breast cancer.
Breast Neoplasms* ; Breast* ; Female ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 1* ; Glucose* ; Humans ; Oncogenes ; Recurrence ; Risk Factors ; Stomach Neoplasms ; Uterine Cervical Neoplasms

PURPOSE: Breast cancer of malignant tumor occurring in domestic women is a tumor frequently seen in the third order following uterine cervical cancer and gastric cancer. This tumor may be recur even following positive treatment, so various methods have been studied to elucidate risk factors for recurrence. In particular, among the various oncogenes concerned in the recurrence of breast cancer, some have been seen as prognostic factors. In a recent study of protein expression in the tumor cell, it was demonstrated that expression increases glucose uptake and utilization, and that Glut1 facilitating the glucose transporter is increased in expression in various tumors of body. Many studies have been conducted on the role of protein in this glucose transporter in breast cancer, yet more studies are required. METHODS: Dye studies were carried out according to an ordinary ABC method utilizing polyclonal anti-Glut1 antibody to detect Glut1 protein in 79 breast cancer samples. RESULTS: Among the 79 breast cancer tissue samples, 41 samples (52%) demonstrated expression of Glut1. Upon close examnination, the expression frequency of Glut1 in brest cancer in relation to existing breast cancer prognosis-related factors, showed a statistically significant correlation with the histologic grade of the breast cancer. CONCLUSION: As Glut1 positive expression was seen in the breast cancer cell, it is suggested that Glut1 is involved in the occurrence of breast cancer. In particular, in poorly differentiated breast cancer, the expression was frequency increased, which suggested its potential as a prognostic factor for breast cancer.
Breast Neoplasms* ; Breast* ; Female ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 1* ; Glucose* ; Humans ; Oncogenes ; Recurrence ; Risk Factors ; Stomach Neoplasms ; Uterine Cervical Neoplasms

PURPOSE: Breast cancer of malignant tumor occurring in domestic women is a tumor frequently seen in the third order following uterine cervical cancer and gastric cancer. This tumor may be recur even following positive treatment, so various methods have been studied to elucidate risk factors for recurrence. In particular, among the various oncogenes concerned in the recurrence of breast cancer, some have been seen as prognostic factors. In a recent study of protein expression in the tumor cell, it was demonstrated that expression increases glucose uptake and utilization, and that Glut1 facilitating the glucose transporter is increased in expression in various tumors of body. Many studies have been conducted on the role of protein in this glucose transporter in breast cancer, yet more studies are required. METHODS: Dye studies were carried out according to an ordinary ABC method utilizing polyclonal anti-Glut1 antibody to detect Glut1 protein in 79 breast cancer samples. RESULTS: Among the 79 breast cancer tissue samples, 41 samples (52%) demonstrated expression of Glut1. Upon close examnination, the expression frequency of Glut1 in brest cancer in relation to existing breast cancer prognosis-related factors, showed a statistically significant correlation with the histologic grade of the breast cancer. CONCLUSION: As Glut1 positive expression was seen in the breast cancer cell, it is suggested that Glut1 is involved in the occurrence of breast cancer. In particular, in poorly differentiated breast cancer, the expression was frequency increased, which suggested its potential as a prognostic factor for breast cancer.
Breast Neoplasms* ; Breast* ; Female ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 1* ; Glucose* ; Humans ; Oncogenes ; Recurrence ; Risk Factors ; Stomach Neoplasms ; Uterine Cervical Neoplasms