• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.147-147
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• 2002

In this study, a mechanism by which glucose level modulates glucose transport in Jurkat cells was investigated. Glucose uptake was more efficient in the cells cultivated in low glucose (2.5 mM) medium than that grown in high glucose (20 $\mu$M) medium. Vmax (0.74 n㏖/10$^6$ cells$\cdot$min) of glucose uptake measured with the cells grown in the low glucose medium was higher than the one (1.06 n㏖/10$^6$ cells$\cdot$min) in the high glucose medium while Km was almost consistent through the change of glucose levels, indicating the increase of glucose transporter number.

• The Korean Journal of Physiology
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• 제29권2호
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• pp.191-202
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• 1995

The purpose of this study was to compare effects of insulin and IGFs on growth, apical membrane enzyme activities and membrane transport systems of primary cultured rabbit kidney proximal tubule cells. Results were as follows: 1. Insulin and IGF-I produced significant growth stimulatory effects at $5{\times}10^{-10}M.\;IGF-II(5×10^{-10}\;M)$ did not stimulate significant cell growth. 2. Insulin stimulated the phosphorylation of a 97 KD protein. It was difficult to determine whether this band represents insulin and/or the IGF-I receptor. 3. The activities of apical membrane enzymes (alkaline phosphatase, leucine aminopeptidase, and ${\gamma}-glutamyl \;transpeptidase)$ were observed to be diminished after the cells were placed in the culture environment. 4. The uptake of ${\alpha}-MG,$ Pi and Na was significantly increased in cells incubated with insulin or IGF-I, IGF-II had no effect on the uptake of these substrates. 5. Na-pump activity, as assayed by Rb uptake, was significantly increased in cells treated with insulin or IGFs. In conclusion, insulin and IGF-I exert stimulatory effects on growth and membrane transporter(glucose, Na, Pi, and Na-pump) activities in primary cultured rabbit kidney proximal tubule cells. IGF-II had no effect on cell growth and membrane transporter(glucose, Na and Pi) activities.

• Asian-Australasian Journal of Animal Sciences
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• 제23권5호
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• pp.640-648
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• 2010

Insulin-responsive glucose transporter 4 (GLUT4) is a member of the glucose transporter family and mainly presents in skeletal muscle and adipose tissue. To clarify the molecular structure of porcine GLUT4, RACE was used to clone its cDNA. Several cDNA clones corresponding to different regions of GLUT4 were obtained by amplifying reverse-transcriptase products of total RNA extracted from Landrace porcine skeletal muscles. Nucleotide sequence analysis of the cDNA clones revealed that porcine GLUT4 cDNA was composed of 2,491 base pairs with a coding region of 509 amino acids. The deduced amino acid sequence was over 90% identical to human, rabbit and cattle GLUT4. The tissue distribution of GLUT4 was also examined by Real-time RT-PCR. The mRNA expression abundance of GLUT4 was heart>liver, skeletal muscle and brain>lung, kidney and intestine. The developmental expression of GLUT4 and insulin receptor (IR) was also examined by Real-time RT-PCR using total RNA extracted from longissimus dorsi (LM), semimembranosus (SM), and semitendinosus (SD) muscle of Landrace at the age of 1, 7, 30, 60 and 90 d. It was shown that there was significant difference in the mRNA expression level of GLUT4 in skeletal muscles of Landrace at different ages (p<0.05). The mRNA expression level of IR also showed significant difference at different ages (p<0.05). The developmental change in the mRNA expression abundance of GLUT4 was similar to that in IR, and both showed a higher level at birth and 30 d than at other ages. However, there was no significant tissue difference in the mRNA expression of GLUT4 or IR (p>0.05). These results showed that the nucleotide sequence of the cDNA clones was highly identical with human, rabbit and cattle GLUT4 and the developmental change of GLUT4 mRNA in skeletal muscles was similar to that of IR, suggesting that porcine GLUT4 might be an insulin-responsive glucose transporter. Moreover, the tissue distribution of GLUT4 mRNA showed that GLUT4 might be an important nutritional transporter in porcine skeletal muscles.

• 약학회지
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• 제48권4호
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• pp.247-253
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• 2004

We investigated the hypoglycemic effect of formula containing Euonymus alatus (EA) and Mori Folium (MF) in multiple low dose (MLD) streptozotocin (STZ)-induced diabetic rats. In order to iduce hyperglycemic state 25 mg/kg of STZ was injected intraperitoneally for 5 consecutive days. SD rats were randomly divided into diabetic control and treatment groups. Treatment groups were administered with either 250 mg/kg of EA and 250 mg/kg of MF (E1Ml), or 500 mg/kg of EA mixed with same dose of MF (E2M2) for 3 weeks. Blood glucose levels and body weights were measured every 5th or 6th day. E1Ml and E2M2 both significantly reduced food intake, water intake, and fasting blood and urine glucose levels as compared to those in diabetic control group in a dose dependent manner. Body weight in diabetic control group was increased slightly after 3 weeks. Treatment group, however, showed gradual increase in body weights during 3 week-period. While plasma insulin levels of the diabetic control group were decreased to the level of 387$\pm$14 pg/ml from 534$\pm$36 pg/ml, those levels in E1Ml and E2M2-treated groups were both markedly increased by 13% and 26%, respectively. Urine glucose levels in E1Ml and E2M2-treated groups were also remarkably reduced by 17 and 26% compared to the levels of diabetic control group. While expression of membrane-bound glucose transporter-4 (GLUT-4) protein in skeletal muscle was reduced by 45% in diabetic control compared to the normal control, GLUT-4 protein expressions in E1Ml and E2M2-treated groups were augmented by 2 and 3.5 times compared to the diabetic control, respectively. Pancreatic HE staining experiments showed that E2M2-treated group revealed much less infiltrated mononuclear cells, indicating that E2M2 efficiently blocked insulitis induced by multiple low dose streptozotocin. Taken together, we conclude that formula containing EA and MF may prevent or delay the development of hyperglycemia through overexpression of GLUT-4 protein in skeletal muscle and prevention of insulitis.

• The Korean Journal of Physiology and Pharmacology
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• 제5권2호
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• pp.183-188
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• 2001

To elucidate antidiabetic effect and mechanism(s) of acarbose in a polygenic spontaneous hyperglycemic and hyperinsulinemic diabetic animal model, $KKA^y$ mice, acarbose was administered orally for 4 weeks and effects on body weight, plasma glucose and insulin levels, genetic expressions of intestinal sucrase-isomaltase (SI), sodium-glucose cotransporter (sGLT1) and glucose transporter in quadriceps muscle (GLUT4) were examined in this study. Although no differences in body weight were detected between control and acarbose-treated groups, plasma glucose level in acarbose-treated group was markedly reduced as compared to the control. In the mechanism study, acarbose downregulated the SI and SGLT1 gene expressions, and upregulated the GLUT4 mRNA and protein expressions when compared to the control group. In conclusion, the data obtained strongly implicate that acarbose can prevent the hyperglycemia in $KKA^y$ mice possibly through blocking intestinal glucose absorption by downregulations of SI and sGLT1 mRNA expressions, and upregulation of skeletal muscle GLUT4 mRNA and protein expressions.

• Journal of Ginseng Research
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• 제35권3호
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• pp.308-314
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• 2011

In the present study, we investigate anti-diabetic effect of pectinase-processed ginseng radix (GINST) in high fat diet-fed ICR mice. The ICR mice were divided into three groups: regular diet group, high fat diet control group (HFD), and GINSTtreated group. To induce hyperglycemia, mice were fed a high fat diet for 10 weeks, and mice were administered with 300 mg/kg of GINST once a day for 5 weeks. Oral glucose tolerance test revealed that GINST improved glucose tolerance after glucose challenge. Compared to the HFD control group, fasting blood glucose and insulin levels were decreased by 57.8% (p<0.05) and 30.9% (p<0.01) in GINST-treated group, respectively. With decreased plasma glucose and insulin levels, the insulin resistance index of the GINST-treated group was reduced by 68.1% (p<0.01) compared to the HFD control group. Pancreas of GINST-treated mice preserved a morphological integrity of islets and consequently having more insulin contents. In addition, GINST up-regulated the levels of phosphorylated AMP-activated protein kinase (AMPK) and its target molecule, glucose transporter 4 (GLUT4) protein expression in the skeletal muscle. Our results suggest that GINST ameliorates a hyperglycemia through activation of AMPK/GLUT4 signaling pathway, and has a therapeutic potential for type 2 diabetes.

• 생명과학회지
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• 제32권2호
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• pp.86-93
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• 2022

Lupeol은 pentacyclic triterpene의 일종으로 다양한 질병에 약리 효과가 있는 것으로 보고되어 있으나, lupeol이 포도당 흡수에 미치는 영향은 아직 보고된 바 없다. 본 연구에서 3T3-L1 지방세포에서 포도당 흡수에 대한 lupeol의 효과를 조사하였다. 그 결과, Lupeol은 3T3-L1 지방세포에서 GLUT4를 원형질막으로 이동시켜 포도당 흡수를 촉진하였으며, 이는 PI3K/AKT 및 AMPK 경로의 활성화와 관련되어 있었다. PI3K/AKT 경로에서 lupeol은 PI3K를 활성화시키는 insulin receptor substrate 1의 인산화와 AKT의 인산화를 촉진하지만 비정형 단백질 키나아제 C isoforms ζ 및 λ의 인산화는 촉진하지 않았다. 반면, lupeol은 5 'AMP-activated protein kinase의 인산화를 촉진하였고, Lupeol의 의한 AMPK의 활성화는 원형질막-GLUT4의 발현과 세포내 포도당 흡수를 증가시키는 것으로 확인되었다. 3T3-L1 지방세포에서 lupeol에 의한 포도당 흡수 효과는 PI3K 억제제인 wortmannin 및 AMPK 억제제인 Compound C에 의해 억제됨을 통해 확인하였다. 본 연구 결과는 lupeol이 3T3-L1 지방세포에서 PI3K/AKT 및 AMPK 경로를 통해 원형질막 GLUT4의 발현을 자극함으로써 인슐린 감수성을 증가시켜 포도당 흡수를 촉진할 수 있음을 제시하고 있다.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.220-225
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• 2012

To develop a ginseng product possessing an efficacy for diabetes, ginseng radix ethanol extract was treated with pectinase and obtained the GINST. In the present study, we evaluate the beneficial effect of GINST on high fat diet (HFD)-induced hyperglycemia and hyperlipidemia and action mechanism(s) in ICR mice. The mice were randomly divided into five groups: regular diet group (RD), high fat diet group (HFD), HFD plus GINST at 75 mg/kg (GINST75), 150 mg/kg (GINST150), and 300 mg/kg (GINST300). Oral glucose tolerance test reveals that GINST improves the glucose tolerance after glucose challenge. Fasting plasma glucose and insulin levels were decreased by 4.3% and 4.2% in GINST75, 10.9% and 20.0% in GINST150, and 19.6% and 20.9% in GINST300 compared to those in HFD control group. Insulin resistance indices were also markedly decreased by 8.2% in GINST75, 28.7% in GINST150, and 36.4% in GINST300, compared to the HFD control group. Plasma triglyceride, total cholesterol and non-esterified fatty acid levels in the GINST300 group were decreased by 13.5%, 22.7% and 24.1%, respectively, compared to those in HFD control group. Enlarged adipocytes of HFD control group were markedly decreased in GINST-treated groups, and shrunken islets of HFD control mice were brought back to near normal shape in GINST300 group. Furthermore, GINST enhanced phosphorylation of AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4). In summary, GINST prevents HFD-induced hyperglycemia and hyperlipidemia through reducing insulin resistance via activating AMPK-GLUT4 pathways, and could be a potential therapeutic agent for type 2 diabetes.

• Journal of Nutrition and Health
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• 제47권3호
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• pp.167-175
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• 2014

본 연구에는 SCLE를 이용하여 시도된 바가 없는 glucose uptake 유도 실험을 수행하여 HepG2 세포에서 포도당흡수가 증가함을 확인하였다. 또한 이런 포도당의 흡수는 HNF-$1{\alpha}$라는 transcription factor의 활성화를 통해 GLUT-2의 발현을 증가시키기 때문인 것을 실험적으로 증명하였다. 뿐만 아니라 Bacillus stearothermophilus 유래의 GK를 이용하여 활성을 측정한 결과 SCLE가 직접적으로 GK를 활성화하여 포도당의 인산화에 영향을 주는 것을 확인할 수 있었으며 그 실험결과들은 Fig. 8에서 도식화 하였다. 본 연구를 통해 SCLE가 ${\alpha}$-glucosidase inhibition 활성에 의한 혈당의 개선과 당뇨예방 효과뿐만 아니라 다양한 세포내 기전을 통해 혈당 및 당뇨의 개선을 유도할 수 있음을 확인하였고, 이는 SCLE가 neutraceuticals 소재로서의 개발가치가 높음을 시사한다.

• 대한의생명과학회지
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• 제15권1호
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• pp.55-60
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• 2009

Insect cells such as Spodoptera frugiperda Clone 9 (Sf9) cells are widely chosen as the host for heterologous expression of a mammalian sugar transport protein using the baculovirus expression system. Characterization of the expressed protein is expected to include assay of its function, including its ability to transport sugars and to bind inhibitory ligands such as cytochalasin B. It is therefore very important first to establish the transport characteristics and other properties of the endogenous sugar transport proteins of the host insect cells. However, very little is known of the transport characteristics of Sf9 cells, although their ability to grow on TC-100 medium strongly suggested the presence of endogenous glucose transport system. In order to investigate the substrate and inhibitor recognition properties of the Sf9 cell transporter, the ability of pentoses to inhibit 2-deoxy-D-glucose (2dGlc) transport was investigated by measuring inhibition constants $(K_i)$. To determine the time period over which of sugar into the Sf cells was linear, the uptake of 2dGlc 0.1mM extracellular concentration was measured over periods ranging from 30 seconds to 30 minutes. The uptake was linear for at least 2 minutes at the concentration, implying that uptake made over a 1 minute time course would reflect initial rates of the sugar uptake. The data have also revealed the existence of a saturable transport system for pentose uptake by the insect cells. The transport was inhibited by D-xylose and D-ribose, although not as effective as hexoses. However, L-xylose had a little effect on 2dGlc transport in the Sf9 cells, indicating that the transport is stereoselective. Unlike the human erythrocyte-type glucose transport system, D-ribose had a somewhat greater apparent affinity for the Sf9 cell transporter than D-xylose. It is therefore concluded that Sf9 cells contain an endogenous sugar transport activity that in some aspects resembled the human erythrocyte-type counterpart, although the Sf9 and human transport systems do differ in their affinity for cytochalasin B.