Expression Of Glucose Transporter Type Research Articles

Comparison of 18F-Fluorodeoxyglucose Uptake with the Expressions of Glucose Transporter Type 1 and Na+/I− Symporter in Patients with Untreated Papillary Thyroid Carcinoma

Purpose. Discrepancies between the uptakes of 18F-fluorodeoxyglucose (18F-FDG) and 131I in papillary thyroid carcinoma have been reported. We compared 18F-FDG uptake with the expressions of glucose transporter type 1 (GLUT1) and sodium-iodide symporter (NIS) in untreated papillary thyroid carcinoma. Materials and methods. A total of 33 consecutive patients (Male:Female = 12:21; mean age, 46.6 ± 13.0 years) with initially diagnosed papillary thyroid carcinoma were prospectively included in the study. All subjects underwent preoperative 18F-FDG positron emission tomography/computerized tomography scans followed by surgery. The expressions of GLUT1 and NIS were evaluated in resected primary tumors and metastatic lymph nodes by immunohistochemical staining and were compared with the maximum standard uptake value of each lesion, respectively. Results. None of the 40 primary tumors showed significant expressions of GLUT1. Significant expressions of NIS were found in 14 primary tumors (35.0%). Among 36 metastatic lymph nodes, only 1 showed GLUT1 expression. Significant expression of NIS was found in 13 (36.1%) metastatic nodes. The maximum standard uptake value of both primary tumors and metastatic nodes with negative expression of NIS was significantly higher than those with a positive expression of NIS (10.6 ± 10.8 vs. 4.9 ± 5.2, p = 0.011). Conclusions. The 18F-FDG uptake of untreated papillary thyroid carcinoma has an inverse correlation with NIS expression. However, GLUT1 expression does not appear to be associated with 18F-FDG uptake in untreated papillary thyroid carcinoma.

Correlation Between FDG Uptake by PET/CT and the Expressions of Glucose Transporter Type 1 and Hexokinase II in Cervical Cancer

The aim of this study was to explore the association between 2-deoxy-2-F18-fluoro-D-glucose uptake and the expressions of glucose transporter type 1 (GLUT-1) and hexokinase II (HK-II) in the lymph nodes of patients with cervical cancer. This prospective study included 20 women with International Federation of Gynecology and Obstetrics stage IB to stage IIA cervical cancer who underwent positron emission tomography (PET)-computed tomography (CT) (PET/CT) before surgical treatment. In 333 dissected lymph nodes (LNs) obtained, we examined the size, tumor involvement, and expressions of GLUT-1 and HK-II. These characteristics were compared with PET/CT and pathological findings. Pathological analysis found that 21% (70) of the 333 surgically dissected LNs were metastatic. Positron emission tomography/CT detected metastasis with 22.8% sensitivity and 98.5% specificity. The levels of GLUT-1 and HK-II expression in false-positive LNs were higher than those in pathologically confirmed negative nodes (P = 0.015 and P = 0.001, respectively). In metastatic LNs, PET/CT-positive nodes were significantly different from PET/CT-negative nodes in mean size (P = 0.043), tumor involvement (P = 0.008), and proportion of GLUT-1-positive tumor cells (P = 0.042). Our results indicate that overexpression of GLUT-1 and HK-II may be related to 2-deoxy-2-F18-fluoro-D-glucose uptake in false-positive tissues on PET/CT. In metastatic lymph nodes, the ability of PET/CT to detect cancer may depend on tumor involvement, lymph node size, and GLUT-1 expression.

Energy metabolism in H460 lung cancer cells: effects of histone deacetylase inhibitors.

BackgroundTumor cells are characterized by accelerated growth usually accompanied by up-regulated pathways that ultimately increase the rate of ATP production. These cells can suffer metabolic reprogramming, resulting in distinct bioenergetic phenotypes, generally enhancing glycolysis channeled to lactate production. In the present work we showed metabolic reprogramming by means of inhibitors of histone deacetylase (HDACis), sodium butyrate and trichostatin. This treatment was able to shift energy metabolism by activating mitochondrial systems such as the respiratory chain and oxidative phosphorylation that were largely repressed in the untreated controls.Methodology/Principal FindingsVarious cellular and biochemical parameters were evaluated in lung cancer H460 cells treated with the histone deacetylase inhibitors (HDACis), sodium butyrate (NaB) and trichostatin A (TSA). NaB and TSA reduced glycolytic flux, assayed by lactate release by H460 cells in a concentration dependent manner. NaB inhibited the expression of glucose transporter type 1 (GLUT 1), but substantially increased mitochondria bound hexokinase (HK) activity. NaB induced increase in HK activity was associated to isoform HK I and was accompanied by 1.5 fold increase in HK I mRNA expression and cognate protein biosynthesis. Lactate dehydrogenase (LDH) and pyruvate kinase (PYK) activities were unchanged by HDACis suggesting that the increase in the HK activity was not coupled to glycolytic flux. High resolution respirometry of H460 cells revealed NaB-dependent increased rates of oxygen consumption coupled to ATP synthesis. Metabolomic analysis showed that NaB altered the glycolytic metabolite profile of intact H460 cells. Concomitantly we detected an activation of the pentose phosphate pathway (PPP). The high O2 consumption in NaB-treated cells was shown to be unrelated to mitochondrial biogenesis since citrate synthase (CS) activity and the amount of mitochondrial DNA remained unchanged.ConclusionNaB and TSA induced an increase in mitochondrial function and oxidative metabolism in H460 lung tumor cells concomitant with a less proliferative cellular phenotype.

Effects of octreotide on glucose transporter type 2 expression in obese rat small intestine

To investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 (GLUT2) in obese rat intestinal mucosa. We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls. The obese rats were separated into an octreotide treated group of 16 rats and an obese group of 15. The intervention group was injected with octreotide at 40 μg/kg body weight every 12 h for 8 d. Rat body weight was measured weekly to calculate Lee's index. After euthanization, maltase and sucrase activities in the small intestine were measured by activity assays, and the fasting plasma glucose level was measured. The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction and Western blotting assays. Body weight, Lee's index, fasting plasma glucose level, maltase activity in small intestinal mucosa, mucosa and apical GLUT2, GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group (605.61 ± 141.00 vs 378.54 ± 111.75, 337.61 ± 10.82 vs 318.73 ± 20.10, 8.60 ± 1.38 vs 7.33 ± 0.70, 156.01 ± 58.81 vs 50.43 ± 30.49, 390 744.2 ± 62 469.21 vs 170 546.50 ± 50 646.14, 26 740.18 ± 3809.60 vs 354.98 ± 57.19, 0.26 ± 0.11 vs 0.07 ± 0.02, and 2.08 ± 0.59 vs 1.27 ± 0.38, respectively, all P < 0.01). Sucrase activity did not differ between the two groups. Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats (508.27 ± 94.39 vs 605.61 ± 141.00, 7.58 ± 1.51 vs 8.60 ±1.38, respectively, all P < 0.05). The intestinal mucosa and apical GLUT2, expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group (269 975.2 ± 53 730.94 vs 390 744.2 ± 62 469.21, 3758.06 ±364.51 vs 26 740.18 ± 3809.60, 0.08 ± 0.02 vs 0.26 ±0.11, and 1.31 ± 0.27 vs 2.08 ± 0.59, respectively, all P < 0.01). High fat diet-induced obesity is associated with elevated intestinal maltase activity, GLUT2 expression, and permanent apical GLUT2 in the small intestinal mucosa of rats. Octreotide can inhibit these effects.

Myocardial infarction in rats causes partial impairment in insulin response associated with reduced fatty acid oxidation and mitochondrial gene expression

Myocardial infarction leads to contractile dysfunction. In patients with diabetes, impaired contractility has been associated with the loss of insulin effects and mitochondrial dysfunction. We assessed cardiac insulin sensitivity and mitochondrial and contractile function in rats after ligation of the left coronary artery. At 2 weeks after left coronary artery ligation, we performed echocardiography in vivo and assessed the substrate use and insulin response in the isolated working heart and the regulation of insulin (Akt, glucose transporter type 4) and mitochondrial signaling (p38 mitogen-activated protein kinase, peroxisome proliferator-activated receptor-γ coactivator 1α, mitochondrial transcription factor A) using polymerase chain reaction and Western blotting. The infarcted hearts were dilated and had a reduced ejection fraction (ejection fraction<50%). The basal glucose oxidation was preserved, but the fatty acid oxidation was significantly reduced. Insulin's effect on substrate oxidation was significantly impaired for both the decrease in fatty acid oxidation and the increase in glucose oxidation. However, insulin-stimulated glucose uptake was normal in the infarcted hearts, consistent with normal insulin-induced phosphorylation of Akt and unchanged mRNA expression of glucose transporter type 4. The impaired oxidative response to insulin was associated with reduced mRNA expression of the genes regulating fatty acid oxidation (long-chain-acyl-coenzyme A dehydrogenase, carnitine palmitoyltransferase 1, peroxisome proliferator-activated receptor-α) and mitochondrial biogenesis (mitochondrial transcription factor A). Although mRNA expression of the mitochondrial master regulator peroxisome proliferator-activated receptor-γ coactivator 1α was normal in the infarcted hearts, the protein expression of its post-transcriptional activator, p38 mitogen-activated protein kinase, was significantly reduced. Myocardial infarction in rats caused partial insulin resistance at the level of substrate oxidation, which was associated with mitochondrial and cardiac contractile dysfunction. Mitochondrial dysfunction was characterized by a reduced capacity to oxidize fatty acids and might have resulted from impaired mitochondrial biogenesis through the lack of p38 mitogen-activated protein kinase.

Expressions of hypoxia-inducible factor 1α and glucose transporter type 1 in psoriatic lesions.

Objective To investigate the expression of glucose transporter type 1(GLUT-1)and hypoxia-inducible factor 1 (HIF-1)α in psoriatic lesions,and to explore their correlations with keratinocyte proliferation.Methods Biopsy specimens were obtained from 30 patients with psoriasis and 20 normal human controls.Immunohistochemistry and Western blotting were used to examine the protein expression of GLUT-1 and HIF-1α in these specimens.Results GLUT-1 and HIF-1α were mainly expressed in the basal layer of the control skin,but throughout the whole epidermis of psoriatic lesions.A significant increase was observed in the expression of GLUT-1 and HIF-1α in psoriatic lesions compared with that in the control skin (botb P＜0.01).In the case of psoriatic lesions,both the expression of GLUT-1 and HIF-1α was positively correlated with that of Ki-67(r=0.70,0.81 respectively,both P＜0.01),and positive correlation was also found between the expression of GLUT-1 and HIF-1α(r=0.85.P＜0.01).Conclusion Our data suggest that uprcgulation Of GLUT-1 and HIF-1α expression in psoriatic lesions might contribute to the proliferation of keratinocytes and psoriasis development. Key words: Psoriasis; Hypoxia-inducible factor 1; Glucose transporter type 1; Cell proliferation; Ki-67

Relationship Between FDG Uptake and Expressions of Glucose Transporter Type 1, Type 3, and Hexokinase-II in Reed-Sternberg Cells of Hodgkin Lymphoma

Reed-Sternberg (R-S) cells are the main tumor cells of Hodgkin lymphoma (HL). HL has been reported to demonstrate a high level of [18F]2-fluoro-2-deoxy-D-glucose (FDG) uptake, but the determinant of FDG uptake for HL has not been well elucidated. Thus, we investigated the relationship of FDG uptake and the expressions of glucose transporter type 1 (Glut-1), glucose transporter type 3 (Glut-3), and hexokinase II (HK-II) in R-S cells of HL. There were 25 tissue-proven HL patients from January 2003 to July 2007 in our hospital. Of the 25 HL patients, 4 cases obtained by surgical excision were included in the present study. The immunostaining for Glut-1, Glut-3, and HK-II was conducted in the excised masses. The maximum standardized uptake values (maxSUVs) were compared to the expressions of Glut-1, Glut-3, and HK-II. Three HL patients (mixed cellularity = 2 and nodular sclerosis = 1) demonstrated moderate-strong expressions of Glut-1 in almost all R-S cells, and of these three HL patients, two underwent FDG-PET, which revealed a high level of maxSUVs (7.7, 6.5) in the corresponding HL lesions. One HL patient (lymphocyte depletion) showed weak Glut-1 expressions in only 10% of R-S cells, but no FDG-PET study was available. The expressions of Glut-3 and HK-II were various in all four HL patients, and no specific correlations with FDG uptake were found. In conclusion, high expressions of Glut-1 in R-S cells may play a crucial role for the high FDG uptake in Hodgkin lymphoma.

Effects of Poly-L-Lysine and Collagen on FH-B-TPN Cell Differentiation Into Endocrine Cell Phenotype

Pdx-1 genetically engineered FH-B-TPN cells might represent a source for insulin-secreting cells. We then have tested whether poly-L-lysine (PLL) and collagen (C) exposure in vitro promote three-dimensional particle formation and differentiation toward an endocrine cell phenotype. On these matrices, we observed that FH-B-TPN cells showed a tendency to either aggregate when seeded on PLL or to form uniform cell monolayers, but not to aggregate on C. While insulin was released in any condition, GSIR was only associated with PLL mainly at 24 and 72 hours of culture. Various culture matrices influenced the expression of glucose transporter type 2 and gluco kinase, being they expressed more intensively on PLL rather than C or in controls. mRNA expression for NeuroD/Beta2, Isl-1, Ras, Metalloproteinase-2 (MMP-2), −9 and −7 also were affected, with PLL inducing increased expression of NeuroD/Beta2 of Isl-1, and no difference between C and control. PLL, unlike C, strongly increased Ras through observation times. MPP-2 and −9 were decreased by both PLL and C, whereas MMP-7 was increased by PLL. PLL, usually employed to promote culture cell adhesion, has been proven capable to stimulate pancreatic endocrine function and cell aggregation and to stimulate gene expression of key markers for either insulin transcription or MMP-7.

Maternal stress alters endocrine function of the feto-placental unit in rats

Prenatal stress (PS) can cause early and long-term developmental effects resulting in part from altered maternal and/or fetal glucocorticoid exposure. The aim of the present study was to assess the impact of chronic restraint stress during late gestation on feto-placental unit physiology and function in embryonic (E) day 21 male rat fetuses. Chronic stress decreased body weight gain and food intake of the dams and increased their adrenal weight. In the placenta of PS rats, the expression of glucose transporter type 1 (GLUT1) was decreased, whereas GLUT3 and GLUT4 were slightly increased. Moreover, placental expression and activity of the glucocorticoid "barrier" enzyme 11beta-hydroxysteroid dehydrogenase type 2 was strongly reduced. At E21, PS fetuses exhibited decreased body, adrenal pancreas, and testis weights. These alterations were associated with reduced pancreatic beta-cell mass, plasma levels of glucose, growth hormone, and ACTH, whereas corticosterone, insulin, IGF-1, and CBG levels were unaffected. These data emphasize the impact of PS on both fetal growth and endocrine function as well as on placental physiology, suggesting that PS could program processes implied in adult biology and pathophysiology.

Regulation of glucose transporter type 4 isoform gene expression in muscle and adipocytes

The gene expression of glucose transporter type 4 isoform (GLUT4) is known to be controlled by metabolic, nutritional, or hormonal status. Understanding the molecular mechanisms governing GLUT4 gene expression is critical, because glucose disposal in the body depends on the activities of GLUT4 in the muscle and adipocytes. The GLUT4 activities are regulated by a variety of mechanisms. One of them is transcriptional regulation. GLUT4 gene expression is regulated by a variety of transcriptional factors in muscle and adipose tissue. These data are accumulating regarding the transcriptional factors regulating GLUT4 gene expression. These include MyoD, MEF2A, GEF, TNF-alpha, TR-1alpha, KLF15, SREBP-1c, C/EBP-alpha, O/E-1, free fatty acids, PAPRgamma, LXRalpha, NF-1, etc. These factors are involved in the positive or negative regulation of GLUT4 gene expression. In addition, there is a complex interplay between these factors in transactivating GLUT4 promoter activity. Understanding the mechanisms controlling GLUT4 gene transcription in these tissues will greatly promote the potential therapeutic drug development for obesity and T2DM.

Glucose transporter type 1 expression are associated with poor prognosis in patients with salivary gland tumors

The objective of this study was to investigate the expression of Glucose transporter type 1 (GLUT1) and its relation to clinicopathologic parameters in patients with salivary gland tumors. Tissue samples were 49 cases of malignant tumors, 38 cases of benign tumors, mainly pleomorphic adenoma and 10 cases of normal salivary glands. Immunohistochemically, GLUT1 Labeling Index of malignant tumor was significantly higher than benign tumor. In RT-PCR assay, GLUT1 mRNA level in malignant tumor were higher than that of normal tissue. In malignant tumors, expression of GLUT1 correlated significantly with tumor size (p=0.002) and distant metastasis (p=0.007). Cumulative survival rate of high expression group was significantly lower than that of low (p<0.001). In multivariable analysis, overall survival significantly correlated with lymph node metastasis (p=0.042) and GLUT1 expression (p=0.022). These results suggest that GLUT1 expression may provide useful prognostic information in patients with salivary gland carcinoma.

Induction of Human T Cell Leukemia Virus Type I Receptors on Quiescent Naive T Lymphocytes by TGF-β

The retrovirus human T cell leukemia virus (HTLV) type I (HTLV-I) is primarily transmitted by breast-feeding or sexual contact, by cell-to-cell contact between T cells. TGF-beta, which has been shown to enhance transmission of HTLV-I in vitro, is found at high levels in breast milk and semen. In this study, the ability of TGF-beta to regulate expression of molecules involved in HTLV-I binding and entry was examined. Previous studies using a soluble form of the HTLV-I envelope protein SU have shown that quiescent human T cells do not express cell surface molecules that specifically bind SU. After T cell activation, HTLV SU binding proteins are rapidly induced. In this study, we report that TGF-beta induces expression of proteins that bind soluble HTLV SU and HTLV virions on naive CD4(+) T lymphocytes. The induction of these proteins occurred without cell cycle entry or expression of activation markers, involved TGF-beta-induced intracellular signaling, and required de novo transcription and translation. Treatment of naive CD4(+) T lymphocytes with TGF-beta induced expression of GLUT-1, which has recently been reported to function as a receptor for HTLV. Treatment of a TGF-beta-sensitive human myeloid cell line increased the titer of both HTLV-I- and HTLV-II-pseudotyped viruses. Although earlier studies suggested that HTLV SU binding proteins might be an early marker of T cell activation and/or cell proliferation, we report in this study that TGF-beta induces binding of HTLV virions and expression of glucose transporter type 1 in primary CD4(+) T lymphocytes that remain quiescent.