• Title/Summary/Keyword: Glucose transporter 1

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Correlation between glucose transporter type-1 expression and $^{18}F$-FDG uptake on PET in oral cancer

  • Kim, Chul-Hwan;Kim, Moon-Young
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.38 no.4
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    • pp.212-220
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    • 2012
  • Objectives: Fluorine-18 fluorodeoxyglucose positron emission tomography ($^{18}F$-FDG PET) is a non-invasive diagnostic tool for many human cancers wherein glucose uptake transporter-1 (GLUT-1) acts as a main transporter in the uptake of $^{18}F$-FDG in cancer cells. Increased expression of glucose transporter-1 has been reported in many human cancers. In this study, we investigated the correlation between $^{18}F$-FDG accumulation and expression of GLUT-1 in oral cancer. Materials and Methods: We evaluated 42 patients diagnosed with oral squamous cell carcinoma (OSCC) and malignant salivary gland tumor as confirmed by histology. 42 patients underwent pre-operative $^{18}F$-FDG PET, with the maximum standardized uptake value ($SUV_{max}$) measured in each case. Immunohistochemical staining was done for each histological specimen, and results were evaluated post-operatively according to the percentage (%) of positive area, intensity, and staining score. Results: For OSCC, $SUV_{max}$ significantly increased as T stage of tumor classification increased. For malignant salivary gland tumor, $SUV_{max}$ significantly increased as T stage of tumor classification increased. For OSCC, GLUT-1 was expressed in all 36 cases. GLUT-1 staining score (GSS) increased as T stage of tumor classification increased, with the difference statistically significant. For malignant salivary gland tumor, GLUT-1 expression was observed in all 6 cases; average GSS was significantly higher in patients with cervical lymph node metastasis than that in patients without cervical lymph node metastasis. Average GSS was higher in OSCC ($11.11{\pm}1.75$) than in malignant salivary gland tumor ($5.33{\pm}3.50$). No statistically significant correlation between GSS and $SUV_{max}$ was observed in OSCC or in malignant salivary gland tumor. Conclusion: We found no statistically significant correlation between GSS and $SUV_{max}$ in OSCC or in malignant salivary gland tumor. Studies on the various uses of GLUT during $^{18}F$-FDG uptake and SUV and GLUT as tumor prognosis factor need to be conducted through further investigation with large samples.

Increased glucose metabolism and alpha-glucosidase inhibition in Cordyceps militaris water extract-treated HepG2 cells

  • Kim, Dae Jung;Kang, Yun Hwan;Kim, Kyoung Kon;Kim, Tae Woo;Park, Jae Bong;Choe, Myeon
    • Nutrition Research and Practice
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    • v.11 no.3
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    • pp.180-189
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    • 2017
  • BACKGROUND/OBJECTIVES: Recent living condition improvements, changes in dietary habits, and reductions in physical activity are contributing to an increase in metabolic syndrome symptoms including diabetes and obesity. Through such societal developments, humankind is continuously exposed to metabolic diseases such as diabetes, and the number of the victims is increasing. This study investigated Cordyceps militaris water extract (CMW)-induced glucose uptake in HepG2 cells and the effect of CMW treatment on glucose metabolism. MATERIALS/METHODS: Colorimetric assay kits were used to determine the glucokinase (GK) and pyruvate dehydrogenase (PDH) activities, glucose uptake, and glycogen content. Either RT-PCR or western blot analysis was performed for quantitation of glucose transporter 2 (GLUT2), hepatocyte nuclear factor 1 alpha ($HNF-1{\alpha}$), phosphatidylinositol 3-kinase (PI3k), protein kinase B (Akt), phosphorylated AMP-activated protein kinase (pAMPK), phosphoenolpyruvate carboxykinase, GK, PDH, and glycogen synthase kinase 3 beta ($GSK-3{\beta}$) expression levels. The ${\alpha}-glucosidase$ inhibitory activities of acarbose and CMW were evaluated by absorbance measurement. RESULTS: CMW induced glucose uptake in HepG2 cells by increasing GLUT2 through $HNF-1{\alpha}$ expression stimulation. Glucose in the cells increased the CMW-induced phosphorylation of AMPK. In turn, glycolysis was stimulated, and glyconeogenesis was inhibited. Furthermore, by studying the mechanism of action of PI3k, Akt, and $GSK-3{\beta}$, and measuring glycogen content, the study confirmed that the glucose was stored in the liver as glycogen. Finally, CMW resulted in a higher level of ${\alpha}-glucosidase$ inhibitory activity than that from acarbose. CONCLUSION: CMW induced the uptake of glucose into HepG2 cells, as well, it induced metabolism of the absorbed glucose. It is concluded that CMW is a candidate or potential use in diabetes prevention and treatment.

Morbidly Obese Patients Treated Obesity and Metabolic Diseases Using Naltrexone/Bupropion Extended Release and Other Drugs of Various Mechanisms (날트렉손/부프로피온 복합제 및 여러 기전의 약물을 이용하여 비만과 동반 대사질환을 치료한 고도비만환자)

  • Cho, Soo Hyun
    • Archives of Obesity and Metabolism
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    • v.1 no.2
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    • pp.83-88
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    • 2022
  • Obesity increases the risk of developing metabolic diseases such as hypertension, type 2 diabetes, hyperlipidemia, and cardiovascular diseases, as well as some cancers. To prevent the occurrence of these diseases and death, it is essential to manage obesity. Though there are several treatments for obesity, lifestyle interventions, such as diet and exercise, and drug therapy are most widely used in clinical practice. Among the anti-obesity drugs available, the weight loss effect of naltrexone/bupropion has been well-proven. We present a case study in which naltrexone/bupropion, a glucagon-like peptide-1 agonist, and a sodium-glucose transporter 2 inhibitor showed significant weight loss and improved metabolic parameters. Additionally, the management of type 2 diabetes and hypertension, which are common diseases in patients with obesity, was also included.

Expressional Analysis of Glucose Transporter Isoforms in the Efferent Ductules of Male Sprague Dawley Rat during Postnatal Development

  • Seo, Hee-Jung;Son, Chan-Wok;Lee, Ki-Ho
    • Reproductive and Developmental Biology
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    • v.33 no.4
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    • pp.211-216
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    • 2009
  • A cell frequently utilizes glucose as a fuel of energy and a major substrate of lipid and protein syntheses. A regulation of glucose movement into and out of the cells is precisely controlled by cooperative works of passive and sodium-dependent active processes. At least 13 glucose cotransporter (Slc2a, GLUT) isoforms involve in passive movement of glucose in cells. The efferent ductules (EDs) play in a number of important functions for maintenance of male fertility. In the present study, using real-time PCR analysis, we determined gene expression of five Slc2a isoforms in the EDs. In addition, we compared expression levels of these Slc2a isoforms according to postnatal development ages, 1 week, 2 weeks, 1 month, and 3 months. Results from the current study showed that expression of Slc2a1, Slc2a3, and Slc2a5 mRNAs reached the highest levels at 1 month of age, followed by a transient decrease at 3 months of age. In addition, the level of Slc2a4 mRNA reminded at steady until 1 month of age and was significantly reduced at 3 months of age, whereas the highest level of Slc2a 8 mRNA was detected at 2 weeks of age. Data from the present study indicate a differential expression of various Slc2a isoforms in the ED according to postnatal ages. Thus, it is believed that glucose movement through the epithelial cells in the ED would be regulated by the coordinated manner among Slc2a isoforms expressed at a given age.

Regulation of glucose and glutamine metabolism to overcome cisplatin resistance in intrahepatic cholangiocarcinoma

  • So Mi Yang;Jueun Kim;Ji-Yeon Lee;Jung-Shin Lee;Ji Min Lee
    • BMB Reports
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    • v.56 no.11
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    • pp.600-605
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    • 2023
  • Intrahepatic cholangiocarcinoma (ICC) is a bile duct cancer and a rare malignant tumor with a poor prognosis owing to the lack of an early diagnosis and resistance to conventional chemotherapy. A combination of gemcitabine and cisplatin is the typically attempted first-line treatment approach. However, the underlying mechanism of resistance to chemotherapy is poorly understood. We addressed this by studying dynamics in the human ICC SCK cell line. Here, we report that the regulation of glucose and glutamine metabolism was a key factor in overcoming cisplatin resistance in SCK cells. RNA sequencing analysis revealed a high enrichment cell cycle-related gene set score in cisplatin-resistant SCK (SCK-R) cells compared to parental SCK (SCK WT) cells. Cell cycle progression correlates with increased nutrient requirement and cancer proliferation or metastasis. Commonly, cancer cells are dependent upon glucose and glutamine availability for survival and proliferation. Indeed, we observed the increased expression of GLUT (glucose transporter), ASCT2 (glutamine transporter), and cancer progression markers in SCK-R cells. Thus, we inhibited enhanced metabolic reprogramming in SCK-R cells through nutrient starvation. SCK-R cells were sensitized to cisplatin, especially under glucose starvation. Glutaminase-1 (GLS1), which is a mitochondrial enzyme involved in tumorigenesis and progression in cancer cells, was upregulated in SCK-R cells. Targeting GLS1 with the GLS1 inhibitor CB-839 (telaglenastat) effectively reduced the expression of cancer progression markers. Taken together, our study results suggest that a combination of GLUT inhibition, which mimics glucose starvation, and GLS1 inhibition could be a therapeutic strategy to increase the chemosensitivity of ICC.

Tazarotene-Induced Gene 1 Interacts with DNAJC8 and Regulates Glycolysis in Cervical Cancer Cells

  • Wang, Chun-Hua;Shyu, Rong-Yaun;Wu, Chang-Chieh;Chen, Mao-Liang;Lee, Ming-Cheng;Lin, Yi-Yin;Wang, Lu-Kai;Jiang, Shun-Yuan;Tsai, Fu-Ming
    • Molecules and Cells
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    • v.41 no.6
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    • pp.562-574
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    • 2018
  • The tazarotene-induced gene 1 (TIG1) protein is a retinoidinducible growth regulator and is considered a tumor suppressor. Here, we show that DnaJ heat shock protein family member C8 (DNAJC8) is a TIG1 target that regulates glycolysis. Ectopic DNAJC8 expression induced the translocation of pyruvate kinase M2 (PKM2) into the nucleus, subsequently inducing glucose transporter 1 (GLUT1) expression to promote glucose uptake. Silencing either DNAJC8 or PKM2 alleviated the upregulation of GLUT1 expression and glucose uptake induced by ectopic DNAJC8 expression. TIG1 interacted with DNAJC8 in the cytosol, and this interaction completely blocked DNAJC8-mediated PKM2 translocation and inhibited glucose uptake. Furthermore, increased glycose uptake was observed in cells in which TIG1 was silenced. In conclusion, TIG1 acts as a pivotal repressor of DNAJC8 to enhance glucose uptake by partially regulating PKM2 translocation.

The Hypoglycemic Effects of Acarviosine-Glucose Modulate Hepatic and Intestinal Glucose Transporters In vivo

  • Chung, Mi-Ja;Lee, Young-Soo;Kim, Byoung-Chul;Lee, Soo-Bok;Moon, Tae-Hwa;Lee, Sung-Joon;Park, Kwan-Hwa
    • Food Science and Biotechnology
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    • v.15 no.6
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    • pp.851-855
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    • 2006
  • Acarviosine-glucose (AcvGlc) is an ${\alpha}$-glucosidase inhibitor and has similar inhibitory activity to acarbose in vitro. We synthesized AcvGlc by treating acarbose with Bacillus stearothermophilus maltogenic amylase and fed C57BL/6J and db/db mice with diets containing purified AcvGlc and acarbose for 1 week. AcvGlc (50 and 100 mg/100 g diet) significantly reduced plasma glucose and triglyceride levels in db/db mice by 42 and 51 %, respectively (p<0.0001). The hypoglycemic and hypotriglyceridemic effects of AcvGlc were slightly, but significantly, greater than those seen with acarbose treatment (p<0.0001) in C57BL/6J mice. In an oral glucose tolerance test, glucose tolerance was significantly improved at all time points (p<0.01). The expression of two novel glucose transporters (GLUTs), GLUT10 and GLUT12, were examined by Western blot analysis. GLUT10 was markedly increased in the db/db livers. After AcvGlc treatment, the expression of hepatic GLUT10 was decreased whereas intestinal GLUT12 was significantly increased in both strains of mice. Our results show that AcvGlc improves plasma lipid and glucose metabolism slightly more than acarbose. Regulation of hepatic GLUT10 and intestinal GLUT12 may be important in controlling blood glucose levels.

The effect of multi-strain probiotics as feed additives on performance, immunity, expression of nutrient transporter genes and gut morphometry in broiler chickens

  • Biswas, Avishek;Dev, Kapil;Tyagi, Pramod K;Mandal, Asitbaran
    • Animal Bioscience
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    • v.35 no.1
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    • pp.64-74
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    • 2022
  • Objective: This study was conducted to investigate the effects of dietary multi-strain probiotic (MSP) (Bacillus coagulans Unique IS2 + Bacillus subtillis UBBS14 + Saccharomyces boulardii Unique 28) on performance, gut morphology and expression of nutrient transporter related genes in broiler chickens. Methods: A total of 256 (4×8×8) day-old CARIBRO Vishal commercial broiler chicks of uniform body weight were randomly distributed into four treatments with 8 replicates each and having eight chicks in each replicate. Four dietary treatments were T1 (negative control-basal diet), T2 (positive control-antibiotic bacitracin methylene disalicylate at 20 mg/kg diet), T3 (MSP at 107 colony-forming unit [CFU]/g feed), and T4 (MSP at 108 CFU/g feed). Results: During 3 to 6 weeks and 0 to 6 weeks, the body weight gain increased significantly (p<0.05) in T3 and T4 groups. The feed intake significantly (p<0.05) reduced from T1 to T3 during 0 to 3 weeks and the feed conversion ratio also significantly (p<0.05) improved in T3 and T4 during 0 to 6 weeks. The humoral and cell mediated immune response and the weight of immune organs were also significantly (p<0.05) improved in T3 and T4. However, significant (p<0.05) dietary effects were observed on intestinal histo-morphometry of ileum in T3 followed by T4 and T2. At 14 d post hatch, the relative gene expression of glucose transporter (GLUT5), sodium-dependent glucose transporter (SGLT1) and peptide transporter (PepT1) showed a significant (p<0.05) up-regulating pattern in T2, T3, and T4. Whereas, at 21 d post hatch, the gene expression of SGLT1 and PepT1 was significantly (p<0.05) downregulated in MSP supplemented treatments T3 and T4. Conclusion: The supplementation of MSP at 107 CFU/g diet showed significant effects with improved performance, immune response, gut morphology and expression of nutrient transporter genes. Thus, the MSP could be a suitable alternative to antibiotic growth promoters in chicken diets.

Pear pomace ethanol extract improves insulin resistance through enhancement of insulin signaling pathway without lipid accumulation

  • You, Mi-Kyoung;Kim, Hwa-Jin;Rhyu, Jin;Kim, Hyeon-A
    • Nutrition Research and Practice
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    • v.11 no.3
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    • pp.198-205
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    • 2017
  • BACKGROUND/OBJECTIVES: The anti-diabetic activity of pear through inhibition of ${\alpha}-glucosidase$ has been demonstrated. However, little has been reported about the effect of pear on insulin signaling pathway in obesity. The aims of this study are to establish pear pomace 50% ethanol extract (PPE)-induced improvement of insulin sensitivity and characterize its action mechanism in 3T3-L1 cells and high-fat diet (HFD)-fed C57BL/6 mice. MATERIALS/METHODS: Lipid accumulation, monocyte chemoattractant protein-1 (MCP-1) secretion and glucose uptake were measure in 3T3-L1 cells. Mice were fed HFD (60% kcal from fat) and orally ingested PPE once daily for 8 weeks and body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and serum lipids were measured. The expression of proteins involved in insulin signaling pathway was evaluated by western blot assay in 3T3-L1 cells and adipose tissue of mice. RESULTS: In 3T3-L1 cells, without affecting cell viability and lipid accumulation, PPE inhibited MCP-1 secretion, improved glucose uptake, and increased protein expression of phosphorylated insulin receptor substrate 1 [p-IRS-1, ($Tyr^{632})$)], p-Akt, and glucose transporter type 4 (GLUT4). Additionally, in HFD-fed mice, PPE reduced body weight, HOMA-IR, and serum lipids including triglyceride and LDL-cholesterol. Furthermore, in adipose tissue, PPE up-regulated GLUT4 expression and expression ratio of p-IRS-1 ($Tyr^{632})/IRS$, whereas, down-regulated p-IRS-1 ($Ser^{307})/IRS$. CONCLUSIONS: Our results collectively show that PPE improves glucose uptake in 3T3-L1 cells and insulin sensitivity in mice fed a HFD through stimulation of the insulin signaling pathway. Furthermore, PPE-induced improvement of insulin sensitivity was not accompanied with lipid accumulation.