• Title/Summary/Keyword: glucose uptake

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Establishment of a [18F]-FDG-PET/MRI Imaging Protocol for Gastric Cancer PDX as a Preclinical Research Tool

  • Bae, Seong-Woo;Berlth, Felix;Jeong, Kyoung-Yun;Suh, Yun-Suhk;Kong, Seong-Ho;Lee, Hyuk-Joon;Kim, Woo Ho;Chung, June-Key;Yang, Han-Kwang
    • Journal of Gastric Cancer
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    • v.20 no.1
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    • pp.60-71
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    • 2020
  • Purpose: The utility of 18-fluordesoxyglucose positron emission tomography ([18F]-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based [18F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake. Materials and Methods: Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [18F]-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake. Results: Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049). Conclusions: This preclinical gastric cancer PDX based [18F]-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.

Inhibitory Effects of Ginseng Total Saponins on Hypoxia-induced Dysfunction and Injuries of Cultured Astrocytes

  • Seong, Yeon-Hee;Kim, Hack-Seang
    • Archives of Pharmacal Research
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    • v.20 no.2
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    • pp.103-109
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    • 1997
  • The effects of ginseng total saponins (GTS) on hypoxic damage of primary cultures of astrocytes were studied. Hypoxia was created by placing cultures in an air tight chamber that was flushed with 95% $N_2/5%CO_2$ for 15 min before being sealed. Cultures showed evidence of significant cell injury after 24 h of hypoxia (increased lactate dehydrogenase (LDH) content in the culture medium, cell swelling and decreased glutamate uptake and protein content). Addition of GTS (0.1, 0.3 mg/ml) to the cultures during the exposure to hypoxic conditions produced dose-dependent inhibition of the LDH efflux. GTS (0.1, 0.3 mg/ml) also produced significant inhibition of the increased cell volume of astrocytes measured by $[^3H]$ O-methyl-D-glucose uptake under the hypoxic conditions. Decreased glutamate uptake and protein content was inhibited by GTS. These data suggest that GTS prevents astrocytic cell injury induced by severe hypoxia in vitro.

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Oryung-san Ameliorates Pioglitazone Side Effects (오령산의 피오글리타존 부작용 경감 효과)

  • Shin, Eun-Jung;Choi, Han-Byul;Han, Eun-Jung;Chung, Sung-Hyun
    • YAKHAK HOEJI
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    • v.51 no.5
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    • pp.307-312
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    • 2007
  • Thiazolidinediones (TZDs) induce insulin sensitization through the activation of PPAR${\gamma}$. However, the undesirable effect such as weight gain was observed. The purpose of this study was to find out an herbal drug that could reduce the side effects of pioglitazone. Among herbal formula that we have searched, oryung-san (OR) inhibited the differentiation of preadipocytes and did not affect on glucose uptake in 3T3-L1 adipocytes. In vitro, glucose uptake assay and Oil Red-O staining in 3T3-L1 adipocytes were conducted. In vivo, pioglitazone (PIO, 30 mg/kg), oryung-san (OR, 300 mg/kg), or pioglitazone co-administered with oryung-san (PIO+OR) were administered orally for 7 weeks in high fat diet (HFD) fed ICR mice and measured the body weight and blood glucose level every week. PIO+OR group significantly reduced body weight gain, triglyceride, and total cholesterol compared to PIO group. In addition, PIO+OR group showed a significant reduction of plasma glucose level (72%) compared to HFD control group. Insulin levels in PIO+OR group was also markedly decreased by 85% and 41% compared to HFD control and PIO group, respectively. Diameter of white adipocytes was decreased in the PIO+OR group compared to that in PIO group. Moreover, PIO+OR group reduced expression of PPAR${\gamma}$ and SREBP1a compared to PIO group. Taken together, oryung-san can improve side effects of pioglitazone, such as weight gain and edema, and shows a synergistic effect in plasma insulin levels.

LPS-Induced Modifications in Macrophage Transcript and Secretion Profiles Are Linked to Muscle Wasting and Glucose Intolerance

  • Heeyeon Ryu;Hyeon Hak Jeong;Seungjun Lee;Min-Kyeong Lee;Myeong-Jin Kim;Bonggi Lee
    • Journal of Microbiology and Biotechnology
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    • v.34 no.2
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    • pp.270-279
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    • 2024
  • Macrophages are versatile immune cells that play crucial roles in tissue repair, immune defense, and the regulation of immune responses. In the context of skeletal muscle, they are vital for maintaining muscle homeostasis but macrophage-induced chronic inflammation can lead to muscle dysfunction, resulting in skeletal muscle atrophy characterized by reduced muscle mass and impaired insulin regulation and glucose uptake. Although the involvement of macrophage-secreted factors in inflammation-induced muscle atrophy is well-established, the precise intracellular signaling pathways and secretion factors affecting skeletal muscle homeostasis require further investigation. This study aimed to explore the regulation of macrophage-secreted factors and their impact on muscle atrophy and glucose metabolism. By employing RNA sequencing (RNA-seq) and proteome array, we uncovered that factors secreted by lipopolysaccharide (LPS)-stimulated macrophages upregulated markers of muscle atrophy and pro-inflammatory cytokines, while concurrently reducing glucose uptake in muscle cells. The RNA-seq analysis identified alterations in gene expression patterns associated with immune system pathways and nutrient metabolism. The utilization of gene ontology (GO) analysis and proteome array with macrophage-conditioned media revealed the involvement of macrophage-secreted cytokines and chemokines associated with muscle atrophy. These findings offer valuable insights into the regulatory mechanisms of macrophage-secreted factors and their contributions to muscle-related diseases.

Effect of Ethanol on $Na^+-P_i$ Uptake in Opossum Kidney Cells: Role of Membrane Fluidization and Reactive Oxygen Species

  • Park, In-Ho;Hwang, Moon-Young;Woo, Jae-Suk;Jung, Jin-Sup;Kim, Yong-Keun
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.5
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    • pp.529-538
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    • 1999
  • This study was undertaken to examine the effect of ethanol on $Na^+ -dependent$ phosphate $(Na^+-P_i)$ uptake in opossum kidney (OK) cells, an established renal proximal tubular cell line. Ethanol inhibited ^Na^+-dependent$ component of phosphate uptake in a dose-dependent manner with $I_{50}$ of 8.4%, but it did not affect $Na^+-independent$ component. Similarly, ethanol inhibited $Na^+-dependent$ uptakes of glucose and amino acids (AIB, glycine, alanine, and leucine). Microsomal $Na^+-K^+-ATPase$ activity was not significantly altered when cells were treated with 8% ethanol. Kinetic analysis showed that ethanol increased $K_m$ without a change in $V_{max}$ of $Na^+-P_i$ uptake. Inhibitory effect of n-alcohols on $Na^+-P_i$ uptake was dependent on the length of the hydrocarbon chain, and it resulted from the binding of one molecule of alcohol, as indicated by the Hill coefficient (n) of 0.8-1.04. Catalase significantly prevented the inhibition, but superoxide dismutase and hydroxyl radical scavengers did not alter the ethanol effect. A potent antioxidant DPPD and iron chelators did not prevent the inhibition. Pyrazole, an inhibitor of alcohol dehydrogenase, did not attenuate ethanol-induced inhibition of $Na^+-P_i$ uptake, but it prevented ethanol-induced cell death. These results suggest that ethanol may inhibit $Na^+-P_i$ uptake through a direct action on the carrier protein, although the transport system is affected by alterations in the lipid environment of the membrane.

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Usefulness of Dynamic $^{18}F-FDG$ PET Scan in Lung Cancer and Inflammation Disease (폐암과 폐 염증성질환의 동적양전자방출단층검사 (Dynamic $^{18}F-FDG$ PET)의 유용성)

  • Park, Hoon-Hee;Roh, Dong-Wook;Kim, Sei-Young;Rae, Dong-Kyeong;Lee, Min-Hye;Kang, Chun-Goo;Lim, Han-Sang;Oh, Ki-Back;Kim, Jae-Sam;Lee, Chang-Ho
    • Journal of radiological science and technology
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    • v.29 no.4
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    • pp.249-255
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    • 2006
  • Purpose: The diagnostic utility of fluorine-18 2-deoxy-D-glucose positron emission tomograhpy ($^{18}F-FDG $PET) for the non-invasive differentiation of focal lung lesions originated from cancer or inflammation disease by combined visual image interpretation and semi-quantitative uptake value analysis has been documented. In general, Standardized Uptake Value(SUV) is used to diagnose lung disease. But SUV does not contain dynamic information of lung tissue for the glucose. Therefore, this study was undertaken to hypothesis that analysis of dynamic kinetics of focal lung lesions base on $^{18}F-FDG$ PET may more accurately determine the lung disease. So we compared Time Activity Curve(TAC), Standardized Uptake Value-Dynamic Curve(SUV-DC) graph pattern with Glucose Metabolic Rate(MRGlu) from Patlak analysis. Methods: With lung disease, 17 patients were examined. They were injected with $^{18}F-FDG$ over 30-s into peripheral vein while acquisition of the serial transaxial tomographic images were started. For acquisition protocol, we used twelve 10-s, four 30-s, sixteen 60-s, five 300-s and one 900-s frame for 60 mins. Its images were analyzed by visual interpretation TAC, SUV-DC and a kinetic analysis(Patlak analysis). The latter was based on region of interest(ROIs) which were drawn with the lung disease shape. Each optimized patterns were compared with itself. Results: In TAC patterns, it hard to observe cancer type with inflammation disease in early pool blood area but over the time cancer type slope more remarkably increased than inflammation disease. SUV-DC was similar to TAC pattern. In the result of Patlak analysis, In time activity curve of aorta, even though inflammation disease showed higher blood activity than cancer, at first as time went by, blood activity of inflammation disease became the lowest. However, in time activity curve of tissue, cancer had the highest uptake and inflammation disease was in the middle. Conclusion: Through the examination, TAC and SUV-DC could approached the results that lung cancer type and inflammation disease type has it's own difference shape patterns. Also, it has outstanding differentiation between cancer type and inflammation in Patlak and MRGlu analysis. Through these analysis methods, it will helpful to separation lung disease.

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The Induction Time of Sucrose Active Transport System during the Phloem Cell Development in Suspension Cultures of Streptantus tortus Cotyledon (Streptanthus tortus 자엽의 배양세포에서 사부세포 발달동안 Sucrose 능동수송계의 유도 시기)

  • Cho, Bong-Heuy
    • Journal of Plant Biotechnology
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    • v.31 no.2
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    • pp.169-173
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    • 2004
  • Parenchyma cells of Streptanthus tortus suspension cultures possessed the different transport system for aldose-formed D-glucose and for ketose-formed D-fructose. $K_{m}$ value for D-glucose and D-fructose were 0.28mM and 15.02mM, respectively. $K_{m}$ value of D-mannose was 0.44 mM which is similar to the D-glucose transport system, but D-mannose was transported also through its own special uptake system. Parenchyma cells possessed the transport system of L-glucose, but the function of L-glucose was not known at all. Protoplast of parenchyma cells possessed only the monosugars transport system, but didn't possess the disugars, sucrose transport system. Early developing phloem protoplasts possessed glucose and sucrose transport system at the same time. On the contrary, in the complete developed phloem cells disappeared preexisted glucose transport system in the parenchyma cells, only new induced sucrose transport system existed.ted.

Effect of Cinnamomum camphora Leaf Fractions on Insulin Action (3T3-L1 지방세포에서 녹나무 잎 추출분획물이 인슐린작용에 미치는 효과)

  • Ko, Byoung-Seob;Lee, Mi-Young;Kim, Ho-Kyoung;Chun, Jin-Mi;Choi, Soo-Bong;Jun, Dong-Wha;Jang, Jin-Sun;Park, Sunmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.9
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    • pp.1336-1343
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    • 2005
  • In the present study, we screened candidates for enhancing insulin action and secretion from Cinnamomum camphora (CC) fractions, in 3T3-L1 adipocytes and Min6 cells by investigating insulin- stimulated glucose uptake and glucose-stimulated insulin secretion, respectively. CC were extracted by $70\%$ ethanol followed by XAD-4 column chromatography with serial mixture solvents of methanol and water, and the fractional extractions were utilized for determining insulin action and secretion, and $\alpha$-glucoamylase suppressing activity, A significant insulin-stimulated glucose uptake was observed in 3T3-L1 adipocytes, giving 0.5 or $5{\mu}g/mL$ of $40\%\;and\;60\%$ methanol fractions plus 0.2 nM insulin, compared to the treatment of DMSO plus 0.2 nM insulin. The treatments of $40\%\;and\;60\%$ methanol fractions plus 0.2 nM insulin reached the glucose uptake of 10 nM insulin treatment. The $40\%$ methanol fraction increased triglyceride accumulation by stimulating differentiation and triglyceride synthesis similar to pioglitazone, PPAR-$\gamma$ agonist. No inhibition of $\alpha$-glucoamylase activity of CC fractions was observed. They did not modulate the insulin secretion capacity In either low or high glucose media. These results suggest that $40\%$ methanol fraction contains a potential insulin sensitizer to have a similar function of PPAR-$\gamma$ agonist. Crude CC extract may improve glucose utilization by enhancing insulin-stimulated glucose uptake without elevating glucose stimulated insulin secretion.