• 한국식품위생안전성학회지
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• 제8권4호
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• pp.195-204
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• 1993

Basolateral and brush border membrane (BLM and BBM) vesicles of renal proximal tubules were prepared from adult male New Zealand White rabbits to evaluate as a potential model for assessment of nephrotoxicity. PAH uptakes using BLMV, glucose and leucine uptakes using BBMV were measured in the rabbits treated cephaloridine. In addition, urinalysis and histopathological studies were performed to investigate the correlationship with membrane vesicle uptakes. The results were as follows: (1) the activite of Na+, K+ -ATPase was enriched 12.3-fold in vasolateral memvrane vesicles (BLMV) and the specific activity of alkaline phosphatase in purified brush border memvrane vesicles (BBMV) was enriched 10.1-fold compared with each of microsomal homogenate. (2) In the uptake experiments, cephaloridine decreased initial and probenecid-sensitive PAH uptakes in BLMV. (3) Cephaloridine tested decreased initial and phlorizin-sensitive glucose uptakes in BBMV. (4) Cephaloridine tested decreased initial and Na+-dependent leucine uptakes in BBMV. (5) Cephaloridine tested significantly increased the urinary excretion of glucose and activity of ${\gamma}$-GTP. (6) Cephaloridine tested caused moderate necrotic changes in renal tubular cells and formation of urinary cast in the lumina of Henle's loop and collecting tubules besides the swelling of renal tubules.

• 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.

• Biomolecules & Therapeutics
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• 제12권2호
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• pp.74-78
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• 2004

Paecilomyces tenuipes, a caterpillar fungus, contains many health-promoting ingredients. Recent reports indicate that consumption of P. tenuipes helps reducing blood sugar content for diabetes. Mechanism for reduction in the circulatory sugar content, however, still remains least understood. Methanolic extraction of P. tenuipes (MPT) was prepared and acetoxyscirpendiol (ASD) was subsequently purified limn MPT. Glucose transporter-1 (GLUT-1) was expressed in the Xenopus oocytes and the effect of MPT or ASD on the expressed GLUT-1 was analyzed according to the uptake of 2-dideoxy-D-glucose (2-DOG). MPT was shown to inhibit GLUT-1 activity significant1y compared to the non-treated control. In the presence of ASD and its derivatives, GLUT-1 activity was greatly inhibited in a dose-dependent manner. Among ASD and its derivatives, AS-1 showed most significant inhibition. Taken together, these results strongly indicate that ASD in P. tenuipes may serve as a functional substance in lowering blood sugar in the circulatory system. ASD and its derivatives can be utilized as inhibitors of GLUT-1.

• 약학회지
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• 제40권2호
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• pp.218-224
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• 1996

This laboratory has recently reported the synthesis and in vitro antitumor activity of PT(II) complexes containing ethylenediamine and diphosphine. In view of the reports of others, cisplatin is toxic to the kidney since the kidney's vulnerability to PT(II) complexes may originate in its ability to accumulate and retain platinum to a greater degree than other organs. The in vitro cytotoxicity of these synthetic PT(II) complexes on the primary cultured proximal tubular cells of rabbit kidney and renal cortical cells of human kidney was investigated. Three endpoints for cytotoxicity tests were evaluated:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), $^3H$-thymidine uptake and the glucose consumption tests. The rank order of sensitivity exhibited $^3H$-thymidine uptake>MTT>glucose consumption test. The agents with diphosphine leaving group were significantly less cytotoxic than cisplatin. Moreover, 1,2-bis(diphenylphosphino)ethane (DPPE) exhibited less cytotoxicity than 1.3-bis (diphenylphosphino)propane (DPPP) against on rabbit and human cultured kidney cells. Based on these results, the decreased nephrotoxicity of these new complexes over cisplatin appeared to be partially attributable to a leaving group of DPPP and DPPE. This novel class of platinum compound represents a valuable lead in the development of a "third-generation" agent.

• 대한한의학방제학회지
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• 제27권3호
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• pp.223-236
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• 2019

Dengropanax morfiferus (D), Broussonitia kazinoki (B), and Cudriania tricuspidata (E), a widely cultivated species in South Korea, has been used as traditional medicine to treat numerous diseases. In this study, we evaluated the antidiabetic effects in a various signaling mechanisms using mixed extract and major component contents were analyzed by HPLC in the combined extracts from Dengropanax morfiferus, Broussonitia kazinoki, and Cudriania tricuspidata (DBCE). DBCE inhibited ${\alpha}$-glucosidase and ${\alpha}$-amylase activation and showed potent antioxidant effects, which are evaluated using DPPH, ABTS, and SOD assay. Cytokines, which are released by inflammatory cells in pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus. DBCE showed the protective effects in RINm5F cells against cytokines-induced damage by suppressing inducible nitric oxide (NO) synthase and COX-2 expression and NO production. Insulin resistance is the primary characteristic of type 2 diabetes. Therefore, the regulatory effect of DBCE on glucose uptake and production are investigated in insulin-responsive human HepG2 cells. DBCE stimulated glucose uptake, prevented Glut2 and phosphor-IRS1 downregulation induced by high glucose (HG, 30 mM). Moreover, DBCE pretreatment diminished glucose levels, PEPCK and G6Pase overexpression provoked by HG. These findings suggest that DBCE might be used for diabetes treatment through alpha-glucosidase or alpha-amylase activity regulation, pancreatic beta cell protection, hepatic glucose sensitivity improvement. Cytokines, which are released by inflammatory cells' infiltrations around the pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus.

• 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.

• 한국콘텐츠학회논문지
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• 제9권4호
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• pp.340-346
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• 2009

리튬은 기저수준의 당수송 활성도에 있어 단지 최소한의 효과만 있고, 반면 인슐린에 대한 민감성을 매우 증가시켜 인슐린에 의해 증가된 당수송 활성도를 증가시키는 것으로 알려져 있다. 또한 리튬은 인슐린의 반응성을 증가시키는 효과도 보이고 있다. 한편, 당수송 과정을 증가시키는 리튬의 효과는 인슐린 자극 당수송에만 국한되는 것이 아니라, 최대하 수준의 근수축에 의한 당수송의 민감성을 증가시키는 것으로 알려져 있다. 하지만 사전실험을 통해 리튬이 최대수준의 근수축에서도 당수송의 활성도가 증가하는 당수송의 반응성의 가능성이 제기되었다. 따라서 본 연구에서는 최대수준의 당유입을 자극하는 근수축에 대해 리튬이 미치는 영향을 조사하여, 리튬이 근수측에 의한 당수송의 반응성도 강화시키는지의 여부를 확인하고자 하였다. 본 연구의 목적에 따라 쥐의 활차근을 분리하여, 당수송을 최대수준으로 활성화시키는 근수축 자극 그리고/혹은 인슐린 자극과 병행하여 리튬을 처치하였다. 그 결과 리튬은 근수축 그리고/혹은 인슐린-자극 당유입을 강화시켜 당수송의 반응성을 향상시키지만, 리튬의 단독 처치는 당수송에 대한 향상에 효과가 매우 적은 것으로 나타났다. 따라서 리튬은 근수축 그리고 혹은 인슐린과의 복합처치를 통해 당수송의 반응성을 증가시킴으로써 인슐린 저항성이나 당뇨 치료에 중요한 역할을 할 수 있는 가능성을 갖는 것으로 사료된다.

• Reproductive and Developmental Biology
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• 제39권4호
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• pp.97-104
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• 2015

Glucose is universal and essential fuel of energy metabolism and in the synthesis pathways of all mammalian cells. Glucose is the one of the major precursors of lactose synthesis using glycolysis result in producing milk fat and protein. During the milk fat synthesis, lipoprotein lipase (LPL) and CD36 are required for glucose uptake. Various morecules such as acyl-CoA synthetase 1 (ACSL1) activity of acetyl-CoA synthetase 2 (ACSS2), ACACA, FASN AGPAT6, GPAM, LPIN1 are closely related with milk fat synthesis. Additionally, glucose plays a major role for synthesizing lactose. Activations of lactose synthesize enzymes such as membranebound enzyme, beta-1,4-galactosyl transferase (B4GALT), glucose-6-phosphate dehydrogenase (G6PD) are changed by concentration of glucose in blood resulting change of amount of lactose production. Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. There are 2 types of glucose transporters which consisted facilitative glucose transporters (GLUT); and sodium-dependent transport, mediated by the Na+/glucose cotransporters (SGLT). Among them, GLUT1, GLUT8, GLUT12, SGLT1, SGLT2 are main glucose transporters which involved in mammary gland development and milk synthesis. However, more studies are required for revealing clear mechanism and function of other unknown genes and transporters. Therefore, understanding of the mechanisms of glucose usage and its regulation in mammary gland is very essential for enhancing the glucose utilization in the mammary gland and improving dairy productivity and efficiency.

• Advances in Traditional Medicine
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• 제7권2호
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• pp.141-149
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• 2007

Madhuca indica has been used ethnomedically in Indian folks. In the present study we have investigated anti-inflammatory, anti-ulcer and hypoglycaemic effect of ethanolic extract (EE) and crude alkaloid extract of Madhuca indica seed cake on albino rats. The study showed that the EE had a significant, dose dependent anti-edematogenic, anti-ulcerogenic and hypoglycaemic activity, whereas the crude alkaloid extract exhibited a significant only. Both the extracts possess dose dependent inhibitory activity on carrageenan-induced edema, inhibiting prostaglandins or mediators involved in prostaglandin synthesis, the second phase of inflammation. The EE was significantly effective in protecting pylorus-ligation-induced gastric ulcers at a higher dose level. The active principle of EE seems to be a selective inhibitor of the COX II (prostaglandin synthesis) without important effect on COX I since, EE exhibited both anti-edematogenic and anti-ulcerogenic effect. The EE was effective in reducing the plasma glucose level in normal albino rats in a dose dependent manner, producing hypoglycaemic effect by stimulating the release of insulin from the ${\beta}-cells$ and/or increasing the uptake of glucose from the plasma.

• Biomolecules & Therapeutics
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• 제12권4호
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• pp.250-256
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• 2004

Cordyceps possesses numerous health-promoting ingredients including hypoglycemic agents. The mechanism for the reduction of circulatory sugar content, however, is still not fully understand. In this study, 4-beta acetoxyscirpendiol (ASD) was purified from the methanolic extracts from fruiting bodies of Paecilomyces tenuipes. Na+/Glucose transporter-1 (SGLT-1) was expressed in the Xenopus oocytes. The effect of ASD on the oocyte expressed SGLT-1 was analyzed utilizing the voltage clamp and 2-deoxy-D-glucose (2-DOG) uptake studies. ASD was shown to significantly inhibit SGLT-1 activity compared to the non-treated control in a dose- dependent manner. In the presense of its two derivatives (diacetoxyscirpenol or 15-acetoxyscirpendiol), SGLT-1 activity was greatly inhibited similarly as ASD. Between ASD derivatives, 15-acetoxyscirepenol showed inhibition equivalent to that of ASD while diacetoxyscirpenol did less degree of inhibition. Insummary , these results strongly indicate that ASD in P. tenuipes may serve as a functional substance in lowering blood sugar in the circulatory system. ASD and its derivatives can be utilized as inhibitors of SGLT-1.