• Preventive Nutrition and Food Science
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• 제16권2호
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• pp.135-141
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• 2011

Inhibition of intestinal glucose uptake is beneficial in reducing the blood glucose level for diabetes. To search for an effective intestinal glucose uptake inhibitor from natural sources, 70 native edible plants, fruits and vegetables were screened using Caco-2 cells and fluorescent D-glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG). A compound that was able to inhibit glucose uptake was isolated from methanol extract of Punica granatum L. and called PG-1a. PG-1a appears to be a phthalic acid-diisononyl ester- like compound (PDE) with molecular weight of 418. The inhibitory effect of PG-1a on intestinal glucose uptake was dose-dependent with 89% inhibition at $100\;{\mu}g$/mL. Furthermore, the intestinal glucose uptake inhibitory effect of PG-1a was 1.2-fold higher than phlorizin, a well known glucose uptake inhibitor. This study suggests that PG-1a could play a role in controlling the dietary glucose absorption, and that PG-1a can effectively improve the diabetic condition, and may be used as an optional therapeutic and preventive agent.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.119-119
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• 1997

Valacyclovir is a L-valyl ester prodrug of acyclovir which is a highly effective and selective antiviral agent in the treatment of herpes virus diseases. Valacyclovir is rapidly and almost completely converted to acyclovir and increases the oral bioavailability of acyclovir three to five fold. However, the intestinal absorption mechanism of valacyclovir is not clear. If the improved absorption mechanism of valacyclovir is fully understood, it will provide a rationale of designing the amino acid ester prodrugs of polar drugs containing hydroxyl group. The main objective of our present study is to characterize the membrane transport mechanism of valacyclovir. Methods : Intestinal absorption of valacyclovir was investigated by using in-situ rat perfusion study and its wall permeability was estimated by modified boundary layer model. The membrane transport mechanism was also investigated through the uptake study in Caco-2 cells and in CHO-hPepTl cells. Results : In the rat perfusion study, the wall permeability of valacyclovir was ten times higher than acyclovir and showed concentration dependency, Valacyclovir also demonstrated a D,L stereo-selectivity with L-isomer having an approximately five-fold higher permeability than D-isomer. Mixed dipeptides and cephalexin, which are transported by dipeptide carriers, strongly competed with valacyclovir for the intestinal absorption, while L-valine did not show any competition with valacyclovir. This indicated that the intestinal absorption of valacyclovir could be dipeptide carrier-mediated. In addition, the competitive uptake study in Caco-2 cells presented that dipeptides reduced the valacyclovir uptake but valine did not. Also, in IC$\sub$50/ study, valacyclovir showed strong inhibition on the $^3$H-gly-sar uptake in CHO-hPepTl cells over-expressing a human intestinal peptide transporter. Taken together, the result from our present study indicated that valacyclovir utilized the peptide transporter for the intestinal absorption.

• 대한핵의학회지
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• 제28권3호
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• pp.357-363
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• 1994

1990년 1월부터 1992년 12월까지 서울대학교병원 소아과 및 소아외과에 황달을 주소로 입원하여 원인이 규명되었던 70명의 환아들에서 $^{99m}Tc$-DISIDA 신티그라피와 초음파검사를 실시하여 다음과 같은 성적을 얻었다. 1) 선천성 담도폐쇄증 30명 전예에서 소장방사능이 관찰되지 않았고 신생아간염 40명 중 31예에서 소장 방사능이 관찰되어 소장방사능의 유무에 따른 선천성 담도폐쇄증의 진단은 예민도 100% 특이도 78%, 정확도는 87%이었다. 2) 소장방사능이 관찰되지 않았던 환아에서 간정체 지표는 선천성 담토폐쇄증 16예가 $1.5{\pm}0.6$으로 신생아간염 7예의 $1.2{\pm}0.2$보다 높았고(p<0.05), 신생아간염의 간정체지표의 2표준편차 상한값인 1.5보다 높은 간정체지표를 보인 경우는 7예로 모두 선천성 담도폐쇄증이었다. 그러나 간정체지표가 1.5 이하인 16명중 9예는 선천성 담도폐쇄증, 7예는 신생아간염으로 이들에서는 간정체지표로 구별되지 않았다. 3) 간기능장애를 나타내는 요소를 분석하였을 때 간섭취도는 선천성 담도폐쇄증과 신생아간염에서 유의한 차이가 없었다. 연령과 간섭취지표는 일정한 상관관계가 없었고 총 빌리루빈치와 간섭취지표는 간섭취도가 정상인 환아의 총빌리루빈치가 상대적으로 낮다는 소견 이외에는 일정한 상관관계가 없었다. 신생아간염에서 소장방사능이 보이는 31예의 연령이 $2.1{\pm}0.7$ 개월로 보이지 않는 9예의 연령평균 $1.7{\pm}0.5$개월 보다 많았다(P<0.01). 4) 간섭취지표와 간정체지표와의 관계는, 간섭취지표가 높을 때 즉 간기능 저하가 심할 때 간정체지표가 높으면 즉 간섭취에이은 간정체가 일정이상 수준이면 신생아간염보다 선천성 담도폐쇄증일 가능성이 높았다. 이상의 결과로 연령이 증가하면 선천성 담도폐쇄증환아의 간기능이상은 진행하지만 신생아간염환아의 간기능장애의 정도는 연령과 무관하여, 간섭취지표로 기능을 평가하고 간정체지표로 판독하면 선천성 담도폐쇄증을 감별할 수 있다고 생각하였다. 그러나 간기능저하가 가볍고 간정체지표가 좋지 않을 때에는 역시 구별되지 않아 다른 검사결과를 참조한 임상판단에 의존하여야 할 것이며 수술적 간담도 조영술의 대상 예로 삼아야 한다고 생각하였다. 이 연구의 결과를 통하여 신생아에서 발생하는 황달의 원인을 규명하는데, $^{99m}Tc$-DISIDA 신티그라피가 유용한 검사법이며, 소장방사능이 관찰되지 않는 경우에는 간정체지표와 간섭취지표와의 관계를 고려하여 간섭취지표보다 간정체지표가 상대적으로 좋을 경우 선천성 담도폐쇄증의 가능성이 높아 감별에 도움되는 소견으로 사용할 수 있을 것으로 생각하였다.

• Nutrition Research and Practice
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• 제10권5호
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• pp.477-486
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• 2016

BACKGROUND/OBJECTIVES: Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS: Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks. Expression of genes related to intestinal fatty acid (FA) uptake and channeling (Cd36, Fatp4, Acsl5, Acbp), intestinal chylomicron synthesis (Mtp, ApoB48, ApoA4), hepatic lipid uptake and channeling (Lrp1, Fatp5, Acsl1, Acbp), hepatic triacylglycerol (TAG) lipolysis and FA oxidation (Atgl, Cpt1a, Acadl, Ehhadh, Acaa1), as well as very low-density lipoprotein (VLDL) assembly (ApoB100) were determined by real-time PCR. RESULTS: In intestine, significantly lower Cd36 mRNA expression (P<0.05) and a tendency of lower ApoA4 mRNA levels (P = 0.07) was observed in PNO-fed mice, indicating that PNO consumption may decrease intestinal FA uptake and chylomicron assembly. PNO consumption tended to result in higher hepatic mRNA levels of Atgl (P = 0.08) and Cpt1a (P = 0.05). Significantly higher hepatic mRNA levels of Acadl and ApoB100 were detected in mice fed PNO diet (P<0.05). These results suggest that PNO could increase hepatic TAG metabolism; mitochondrial fatty acid oxidation and VLDL assembly. CONCLUSIONS: PNO replacement in the diet might function in prevention of excessive lipid uptake by intestine and improve hepatic lipid metabolism in both control diet and HFD fed mice.

• Journal of Pharmaceutical Investigation
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• 제25권2호
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• pp.137-143
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• 1995

The peptide transporter can be utilized for improving the bioavailability of compounds that are poorly absorbed. Characterization of the dipeptide uptake into the human intestinal epithelial cells, HT-29 was investigated. The uptake of tritiated glycylsarcosine $([^3H]-Gly-Sar,\;0.1\;{\mu}Ci/ml)$ was measured in confluent or subconfluent HT-29, Caco-2, and Cos-7 cells. Uptake medium was the Dulbecco's Modified Eagle's Media (DMEM) adjusted to pH 6.0. Both HT-29 and Caco-2 cells expressed the dipeptide transporter significantly (p<0.005) but Cos-7 did not. Certain portions of passive uptake were observed in all three cell lines. Uptake of Gly-Sar was largest at 7 days after plating HT-29 cells with significant inhibition with 25 mM cold Gly-Sar (p<0.05). but expression ratio of the dipeptide transporter was 0.7, suggesting lower expression. The effect of pH on Gly-Sar uptake was not significant in the range of pH 6 to 8. Gly-Sar uptake was also inhibited with 50 mM carnosine, 25 mM Gly-Sar, and 35 mM cephalexin significantly (p<0.05). From above results the dipeptide transporter was expressed well in HT-29 cells and was similar to that in the small intestine, suggesting that large amounts of mRNA of the transporter from the cells can be obtained.

• Journal of Pharmaceutical Investigation
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• 제39권3호
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• pp.155-159
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• 2009

In vitro intestinal uptake of non-soluble polystyrene microspheres (NPMS) was visualized with and without oleic acid using a fluorescence microscopy. Fluorescent polystyrene latex microspheres with 1${\mu}$m larger size were used as models for nonspecifically absorbed nonbiodegradable particulates. The NPMS could not penetrate the enterocytes but a few NPMS could be penetrated via Peyer's patches. When the oleic acid was mixed with NPMS, the transporting efficiency of NPMS through enterocytes as well as Peyer's patches was significantly enhanced. The modification of the intestinal membrane permeability and surface feature of the NPMS in the presence of oleic acid might be a clue to the transport of NSPM although the detailed mechanism is still under investigation.

• Journal of Nutrition and Health
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• 제34권2호
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• pp.150-157
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• 2001

Intestinal absorption of dietary taurine is one of the regulatory component maintaining taurine homeostasis along with renal reabsorption, bile acid conjugation and secretion, and de nobo synthesis of taurine in mammals. Recent observations of decreased enterocytic levels of taurine in response to trauma, infection and surgical insults, postulate the possibility that intestinal taurine absorption might be impaired in such stressed conditions. The aim of the present study was to evaluate changes in enterocytic taurine transporter activity using the human intestinal colon carcinoma cell line, HT-29, in various stress-induced conditions. Pretreatment of the HT-29 cells with dexamethasone, a stress hormone(0.1,1,10 or 100$\mu$M) for 3 hrs, or with E coli heat-stable enterotoxin(10, 100, or 200nM) for 30 minutes in order to induce the condition of enterotoxigenic infection did not influence taurine uptake as compared to the value found in control cells. In contrast, pretreatment of the cells with cholera toxin(10, 100, 500, or 1000ng/ml)for 3hr or 24hr significantly decreased taurine uptake by HT-29 cells to 40~50% of the value found in untreated control cells. Kinetic studies of the taurine transporter activity were conducted in control and cholera toxin treated HT-29 cells with varying taurine concentrations(2~60$\mu$M) in the uptake medium. Pretreatment of the cells with cholera toxin(100ng/ml) for 3hr did not influence the Vmax, but resulted in a 55% increase in the Michaelis-Menten constant(Km) of the taurine transporter compared to those in control cells. These results suggest that cholera toxin-induced reduction in taurine transporter activity in HT-29 cells is associated with decreased affinity of the taurine transporter without altering the amount of transporter protein. Intestinal taurine absorption appears to be reduced in the condition of water-borne diseases caused by bacteria such as V. cholerae. This might influence the taurine status of infants and young children more readily, an age group in which the prevalence of intestinal infection is high and the role of intestinal absorption is crucial for maintaining the body taurine pool. (Korean J Nutrition 34(2) : 150-157, 2001)

• Journal of Nutrition and Health
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• 제35권4호
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• pp.446-453
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• 2002

본 논문에서는 자혈양근탕 (滋血養筋湯, JH) 및 양혈장 근건보환 (養血壯筋健步丸, YH) 처방제가 장내 칼슘흡수에 미치는 영향을 살펴보고자 인체 소장상피세포주 모델인 Caco-2 세포를 이용하여 칼슘 uptake와 net transport를 각기 평가하였으며. 그 결과를 요약하면 다음과 같다. 첫째, Caco-2 세포를 분주 후 4, 8, 16. 그리고 24일간 배양하면서 칼슘 uptake 활성을 측정 한 결과 분화가 진행될수록 uptake 활성이 증가하였다. 둘째. Caco-2 세포에 한약처방제를 50 $\mu\textrm{g}$/ml 농도로 일정시간 동안 전처리하여 칼슘 uptake 활성을 측정한 결과, YH 처방제는 24시간 전처리 시 (29.9% 증가), 그리고 JH처방제는 6시간 전처리 시 (23.9%증가) 한약처방으로 전처리하지 않은 대조세포에 비해 칼슘 uptake가 유의적으로 증가하였다. 셋째. 한약처방의 농도를 달리하면서 6시간 동안 전처리한 후 칼슘 Uptake활성을 측정한 결과, 대조세포에 비해 YH 또는 JH 처방제는 100 $\mu\textrm{g}$/ml (23% 증가) 및 50 $\mu\textrm{g}$/ml 농도 (28.3% 증가)에서 칼슘 uptake 활성을 각기 최대로 증가시켰다. 넷째, YH 또는 JH 처방제가 Caco-2 세포에 의한 칼슘 net transport에 미치는 영향을 평가하기 위해 5, 50, 100 $\mu\textrm{g}$/ml농도의 한약처방제로 6시간동안 Caco-2세포에 전처리한 결과, 두가지 한약처방제 모두 칼슘 net transport에 유의적인 변화를 초래하지 않았다. 이상의 in vitro연구결과는 양혈 및 양근작용에 관여하는 자혈양근탕 및 양혈장근건보환 처방제가 소장상피세포를 통한 칼슘 uptake 활성은 증가시킨 한편 칼슘 net transport 활성에 변화를 초래하지 않았고. 결과적으로 장내 칼슘 흡수에 유의적인 영향을 미치지 않았음을 제시하는 것이다

• Food Science and Biotechnology
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• 제17권3호
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• pp.564-568
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• 2008

The effects of sodium copper chlorophyllin (SCC) on bioaccessibility and uptake of mercury from fish were investigated using an in vitro digestion coupled with a Caco-2 cell. Fish along with SCC was subjected to a simulated in vitro digestion, which simulates both the gastric and small intestinal phase in vivo. Mercury bioaccessibility, the amount of mercury released from fish to aqueous phase following a digestion, was measured. Various amounts of SCC (0.1-25 mg) significantly reduced mercury bioaccessibility in a dose dependent manner by 49-89% compared to the negative control (fish without SCC) (p<0.05). Mercury bioaccessibility in varying molar ratios of mercury to positive control, 2,3-dimercapto-1-propane sulfonate (DMPS) was between 24 and 52%. Mercury uptake by Caco-2 cells from test media containing aqueous phase following in vitro digestion was measured after 6 hr incubation at $37^{\circ}C$. Cellular mercury uptake with increasing amount of SCC ranged from 0.352 to $0.052\;{\mu}g$ mercury/mg protein, while those in DMPS treatment were between 0.14 and $0.27\;{\mu}g$ mercury/mg protein. Our study suggests that SCC can reduce mercury absorption following fish consumption and may be efficient as a synthetic chelating agent for long term chronic mercury exposure in fish eating populations.

• 대한핵의학회지
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• 제27권2호
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• pp.315-318
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• 1993

We experienced 7 cases of patients who were performed $^{99m}Tc$-methylene diphosphonate bone scintigraphy for the evaluation of diseases they had. Their bone scintigrams showed incidental radionuclide uptake in the gastrointestinal tracts and they had no special symptom or sign attributable to the findings. Case 1 showed radionuclide uptake in the stomach and both lung and the patient had suffered from hypercalcemia and azotemia. Case 3 and case 6 showed diffuse radionuclide uptake in the stomach and intestinal tract. Others showed diffuse or regional radionuclide uptake in the intestinal tracts. Radionuclide uptake in the gastrointestinal tract by $^{99m}Tc$-methylene diphosphonate is caused by a certain pathologic lesion but also can be seen in the normal gastrointestinal tract. So, one who reads bone scintigrams should be alert for the pathologic lesion in the gastrointestinal tract although one must interpretate with the concept of this normal variations.