• BMB Reports
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• 제30권4호
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• pp.240-245
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• 1997

Interactions between ganglioside $G_{M3}$ and glucose transporter, GLUT1 were studied by measuring the effect of $G_{M3}$ on steady-state and time-resolved fluorescence of purified GLUT1 in synthetic lipids and on the 3-O-methylglucose uptake by human erythrocytes. The intrinsic tryptophan fluorescence showed a GLUT 1 emission maximum of 335 nm, and increased in the presence of $G_{M3}$ by 12% without shifting the emission maximum, The fluorescence lifetimes of intrinsic tryptophan on GLUT1 consisted of a long component of 7.8 ns and a short component of 2,3 ns and $G_{M3}$ increased both lifetime components. Lifetime components were quenched by acrylamide and KI. Acrylarnide-mduced quenching of long-lifetime components was partly recovered by $G_{M3}$ However. KI-induccd quenching of short- and long-lifetime components was not rescued by $G_{M3}$. The anisotropy of 1.6-diphenyl-1.3.5-hexatriene (DPH)-probed dimyristoylphosphatidylcholine (DMPC) model membrane was also increased with $G_{M3}$ incorporation, The transport rate of 3-O-methylglucose increased by 20% with $G_{M3}$ incorporation on the erythrocytes, Therefore, $G_{M3}$ altered the environment of lipid membrane and induced the conformational change of GLUT1.

• Asian-Australasian Journal of Animal Sciences
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• 제15권8호
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• pp.1210-1214
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• 2002

The large and rapid changes of glucose utilization in lactating mammary tissue in response to changes in nutritional state must be largely related by external signal of insulin. This also must be related with the quantity and composition of the diet in vivo. To characterize the mode of gut extract protein with insulin, in vitro experiment was conducted with HC11 cells. The gut extract protein has not only the same effect as insulin alone but also the synergistic effect with insulin in 2-Deoxy[3H] glucose uptake. Although the gut extract did not modulates glucose uptake via increasing the rate of translation of the GLUT1 protein, northern blot analysis indicated that the gut extract protein increased the expression of GLUT1 mRNA by a threefold and also there was a dose-dependent increase in the expression of GLUT1 mRNA. The gut extract protein is therefore shown to be capable of modulating glucose uptake by transcription level with insulin in HC 11 cells.

• 대한핵의학회지
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• 제33권1호
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• pp.1-10
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• 1999

Cancer cells are known to show increased rates of glycolysis metabolism. Based on this, PET studies using F-18-fluorodeoxyglucose have been used for the detection of primary and metastatic tumors. To account for this increased glucose uptake, a variety of mechanisms has been proposed. Glucose influx across the cell membrane is mediated by a family of structurally related proteins known as glucose transporters (Gluts). Among 6 isoforms of Gluts, Glut-1 and/or Glut-3 have been reported to show increased expression in various tumors. Increased level of Glut mRNA transcription is supposed to be the basic mechanism of Glut overexpression at the protein level. Some oncogens such as src or ras intensely stimulate Glut-1 by means of increased Glut-1 mRNA levels. Hexokinase activity is another important factor in glucose uptake in cancer cells. Especially hexokinase type II is considered to be involved in glycolysis of cancer cells. Much of the hexokinase of tumor cells is bound to outer membrane of mitochondria by the porin, a hexokinase receptor. Through this interaction, hexokinase may gain preferred access to ATP synthesized via oxidative phosphorylation in the inner mitochondria compartment. Other biologic factors such as tumor blood flow, blood volume, hypoxia, and infiltrating cells in tumor tissue are involved. Relative hypoxia may activate the anaerobic glycotytic pathway. Surrounding macrophages and newly formed granulation tissue in tumor showed greater glucose uptake than did viable cancer cells. To expand the application of FDG PET in oncology, it is important for nuclear medicine physicians to understand the related mechanisms of glucose uptake in cancer tissue.

• Clinical Nutrition Research
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• 제12권3호
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• pp.169-176
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• 2023

Glucose transporter type 1 (GLUT1) deficiency syndrome (DS) is a metabolic brain disorder caused by a deficiency resulting from SLC2A1 gene mutation and is characterized by abnormal brain metabolism and associated metabolic encephalopathy. Reduced glucose supply to the brain leads to brain damage, resulting in delayed neurodevelopment in infancy and symptoms such as eye abnormalities, microcephaly, ataxia, and rigidity. Treatment options for GLUT1 DS include ketogenic diet (KD), pharmacotherapy, and rehabilitation therapy. Of these, KD is an essential and the most important treatment method as it promotes brain neurodevelopment by generating ketone bodies to produce energy. This case is a focused study on intensive KD nutritional intervention for an infant diagnosed with GLUT1 DS at Gangnam Severance Hospital from May 2022 to January 2023. During the initial hospitalization, nutritional intervention was performed to address poor intake via the use of concentrated formula and an attempt was made to introduce complementary feeding. After the second hospitalization and diagnosis of GLUT1 DS, positive effects on the infant's growth and development, nutritional status, and seizure control were achieved with minimal side effects by implementing KD nutritional intervention and adjusting the type and dosage of anticonvulsant medications. In conclusion, for patients with GLUT1 DS, it is important to implement a KD with an appropriate ratio of ketogenic to nonketogenic components to supply adequate energy. Furthermore, individualized and intensive nutritional management is necessary to improve growth, development, and nutritional status.

• The Korean Journal of Physiology
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• 제25권2호
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• pp.115-123
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• 1991

Molecular association of glucose transporters with the other proteins in the plasma membrane was assessed by gel electrophoresis and immunoblot techniques. Approximately $31.5{\pm}5.1%$ of GLUT-4, $64.8{\pm}2.7%$ of clathrin, 48.7% of total protein in the plasma membrane (PM) were found insoluble upon extraction with 1% Tx-100. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that the Tx-100 insoluble PM fraction contained about 4 major polypeptides with apparent molecular weight of above 200, 100-120, 80 and 30-35 KDa that were readily removed upon wash with a high pH buffer which is known to remove clathrin and 0.5 M Tris-buffer which is known to remove assembly proteins (AP). Immunoblotting of GLUT4 and clathrin against specific antibodies showed that GLUT-4 and clathrin were co-solubilized up to 84.6% and 82.7% respectively by wash with a high pH buffer and 1% Tx-100. When the membrane was pre-washed with a high pH buffer and 0.5 M Tris solution, GLUT4 and clathrin were not solubilized further suggesting that GLUT4 molecules are in molecular association with clathrin, AP and/or other extrinsic membrane proteins in plasma membrane and the formation of clathrin-coated structures might be involved in insulin stimulated glucose transporter translocation mechanism.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7037-7041
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• 2014

Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

• The Korean Journal of Physiology
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• 제30권2호
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• pp.231-236
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• 1996

In our previous study (Kim et al, 1991), GLUT 4 protein content correlated negatively with plasma glucose levels in skeletal muscles of STZ-induced diabetic rats. Thus, in this study, to confirm whether expression of GLUT 4 correlate negatively with degree of hyperglycemia, we measured levels of GLUT 4 mRNA in red and white gastrocnemius muscles in STZ-induced mild and severe diabetic rats. Rats were randomly assigned to control, mild, and severe diabetic groups, and the diabetes was induced by intraperitoneal administration of STZ. The experiment was carried out 10 days after STZ administration. Gastrocnemius red and white muscles were used fur the measurement of GLUT 4 expression. Plasma glucose levels of mild and severe diabetic rats were increased compared to control rats (control, mild, and severe diabetes; $6.4{\pm}0.32,\;9.4{\pm}0.68,\;and\;22.0{\pm}0.58$ mmol/L, respectively). Plasma insulin levels of mild and severe diabetic rats were decreased compared to control rats (control, mild, and severe diabetes; $198{\pm}37,\;l14{\pm}14,\;and\;90{\pm}15$ pmol/L, respectively). GLUT 4 mRNA levels of gastrocnemius red muscles in mild and severe diabetic rats were decreased compared to control rats ($64{\pm}1.2%\;and\;71{\pm}2.0%$ of control, respectively), but GLUT 4 mRNA levels in gastrocnemius white muscles were unaltered in diabetic rats. In summary, GLUT 4 mRNA levels were decreased in STZ-induced diabetic rats but did not correlated negatively with degree of hyperglycemia, and this result suggest that the regulatory mechanisms of decreased GLUT 4 mRNA levels are hypoinsulinemia and/or other metabolic factor but not hyperglycemia. And regulation of GLUT 4 expression in STZ-induced diabetes between red and white enriched skeletal muscles may be related to a fiber specific gene regulatory mechanism.

• Journal of Nutrition and Health
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• 제54권6호
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• pp.603-617
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• 2021

혈당 조절에 유익한 천연 식품을 발굴하고 그 효과를 밝혀보고자 본 연구에서는 아마란스 종자에 주목하여 몇 가지 혈당조절 연관 지표의 증감 정도를 알아보았다. 아마란스 종자의 색과 발아 여부에 따라 효능에 차이가 있는지 알아보기 위하여 발아 흑색 아마란스는 germinated black amaranth (GBA), 비발아 흑색 아마란스는 black amaranth (BA), 발아 황색 아마란스는 germinated yellow amaranth (GYA), 비발아 황색 아마란스는 yellow amaranth (YA)로 구분하였고 각각의 시료는 80% 에탄올 추출물을 만들어 사용하였다. 본 연구에서 α-amylase 및 α-glucosidase 저해 활성을 측정한 결과 GBA, BA, GYA, YA 순으로 높은 저해 활성을 나타냈으며 특히 α-amylase 저해 활성 실험에서 GBA는 양성 대조물질인 acarbose와 거의 비슷한 수준을 나타내어 높은 저해 활성을 가지는 것으로 판단된다. HepG2 세포에서 포도당 흡수를 측정한 결과 모든 추출물에서 농도 의존적으로 증가하였고 GBA > BA > GYA > YA 순으로 높게 나타났다. 특히 50 ㎍/mL 농도에서 GBA는 인슐린과 유사한 값을 나타내었다. GBA를 농도별로 처리한 HepG2 세포에서 ACC, GLUT-2, GLUT-4, IRS-1, IRS-2 mRNA 발현 정도는 모두 농도 의존적으로 증가하였다. 이상의 결과로 아마란스 종자는 혈당 조절 및 개선에 효능이 있다고 평가되며 특히 발아한 흑색 종자가 혈당 조절 효능이 높게 나타남을 보여 혈당 조절에 유익한 효능을 가지는 식품 소재가 될 수 있음을 확인하였다.

• 대한임상전기생리학회지
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• 제1권1호
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• pp.73-85
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• 2003

The purpose of this study is to discuss and analyze the change of GLUT-4 and muscle fiber type of streptozotocin(STZ)-diabetic rats over a period of 6 weeks. We divided into four groups; I(aquatic exercise and feeding of Cordyceps militaris; n=6), test group II(feeding of Cordyceps miliaris; n=6), test group III(aquatic exercise; n=6), control group IV(non-treatment; n=6). After experimenting we measured the blood glucose, body weight, muscle fiber type and GLUT-4 protein content. The change of glucose levels decreased greater in group I than the other group. The body weight gain was lower in the all groups. The change femoris muscle fiber type, the size of muscle fiber TypeII lessened more than the one of Type I in group IV. Decrease of muscle fiber size more diminishment in group I than the other group. GLUT-4 protein quantity decrease in group IV compared to normal group. It was significantly increased in group. I, III compared to group IV. But there was more increase in group I (p<.001). These results suggest that GLUT-4 and muscle fiber type II decrease in STZ-diabetic rats and that when we apply aquatic exercise and feeding of Cordyceps militaris in diabetic rats over a period 6 weeks, it is increase GLUT-4 and the increase of insulin sensitivity of peripheral tissue. So it is considered to be helpful in improvement of glucose homeostasis and in prevent from muscle atrophy resulted from complication.

• 대한핵의학회지
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• 제34권4호
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• pp.294-302
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• 2000

목적: 종양세포에서 F-18-FDG 섭취 기전을 규명하기 위하여 F-18-FDG 섭취와 포도당운반체-1 (Glut-1), hexokinase의 발현과의 상관관계를 조사하였다. 대상 및 방법: 사람의 대장암(SNU-C2A, SNU-C4, SNU-C5), 간암(SNU-387, SNU-423, SNU-449), 폐암(NCI-H522, NCI-H358, NCI-H1299), 자궁경부암(HeLa, HeLa 229, HeLa S3), 그리고 뇌암(A172, Hs 683)에서 기원한 암 세포주 $5{\times}10^5$ 세포를 24 well plate에 24시간 배양하였다. 여기에 37 kBq의 F-18-FDG를 첨가한 후 각 세포의 섭취 정도를 감마 카운터를 사용하여 측정하였다. Hexokinase의 활성은 분광광도계를 사용하여 측정하였다. 디토콘드리아에서의 hexokinase 활성은 고속원심분리기를 이용하여 미토콘드리아 분획을 분리하여 조사하였다. Glut-1의 발현은 면역조직염색법으로 측정하였다. 결과: 종양세포의 종류에 따라 F-18-FDG 섭취, 전체 그리고 미토콘드리아 hexokinase 활성, 그리고 Glut-1의 발현 정도에 차이가 있었다. 종양세포주에서 F-18-FDG 섭취와 세포전체, 세포내 미토콘드리아 hexokinase 활성과의 상관관계(각각 r=0.27, r=0.26)는 낮게 나타났으며, Glut-1의 발현은 F-18-FDG의 섭취와 상관관계(p=0.81, p=0.0015)가 높았다. 대장암 세포주에서 F-18-FDG 섭취와 hexokinase 활성의 상관관계가 없다는 보고를 토대로 대장암 세포주 결과를 제외했을 경우에 F-18-FDG의 섭취와 세포전체 그리고 세포내 미토콘드리아에서의 hexokinase 활성과는 높은 상관관계(각각 r=0.81, p=0.0027, 그리고 r=0.81, p=0.0049)를 보였다. 결론: Glut-1이나 hexokinase 활성이 사람 종양 세포주에서 F-18-FDG의 섭취를 결정하는 주 요인이며, 종양세포의 종류에 따라 이들의 기여도는 서로 다름을 알 수 있었다.