• 제목/요약/키워드: substrate uptake

검색결과 130건 처리시간 0.022초

Ginsenoside Rb1 and compound K improve insulin signaling and inhibit ER stress-associated NLRP3 inflammasome activation in adipose tissue

  • Chen, Weijie;Wang, Junlian;Luo, Yong;Wang, Tao;Li, Xiaochun;Li, Aiyun;Li, Jia;Liu, Kang;Liu, Baolin
    • Journal of Ginseng Research
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    • 제40권4호
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    • pp.351-358
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    • 2016
  • Background: This study was designed to investigate whether ginsenoside Rb1 (Rb1) and compound K (CK) ameliorated insulin resistance by suppressing endoplasmic reticulum (ER) stress-induced inflammation in adipose tissue. Methods: To induce ER stress, epididymal adipose tissue from mice or differentiated 3T3 adipocytes were exposed to high glucose. The effects of Rb1 and CK on reactive oxygen species production, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation, insulin signaling activation, and glucose uptake were detected by western blot, emzyme-linked immunosorbent assay, or fluorometry. Results: Rb1 and CK suppressed ER stress by dephosphorylation of $IRE1{\alpha}$ and PERK, thereby reducing TXNIP-associated NLRP3 inflammasome activation in adipose tissue. As a result, Rb1 and CK inhibited IL-$1{\beta}$ maturation and downstream inflammatory factor IL-6 secretion. Inflammatory molecules induced insulin resistance by upregulating phosphorylation of insulin receptor substrate-1 at serine residues and impairing insulin PI3K/Akt signaling, leading to decreased glucose uptake by adipocytes. Rb1 and CK reversed these changes by inhibiting ER stress-induced inflammation and ameliorating insulin resistance, thereby improving the insulin IRS-1/PI3K/Akt-signaling pathway in adipose tissue. Conclusion: Rb1 and CK inhibited inflammation and improved insulin signaling in adipose tissue by suppressing ER stress-associated NLRP3 inflammation activation. These findings offered novel insight into the mechanism by which Rb1 and CK ameliorate insulin resistance in adipose tissue.

리포솜 봉입이 로다민 123의 소장 흡수에 미치는 영향 (Effect of Liposome Encapsulation on Intestinal Absorption of Rhodamine 123)

  • 홍순선;이해리;이홍;정석재;김대덕;심창구
    • 약학회지
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    • 제49권2호
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    • pp.185-191
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    • 2005
  • The absorption of a P-gp substrate, rhodamine 123, from a liposomal dosage form was investigated across Caco-2 cell monolayers, rat intestines and rat intestinal Peyer's patches in Ussing chamber, Rhodamine 123 was incorporated into liposomes according to the standard evaporation method, which led to a production of liposomes with a mean diameter of 71.3 nm. The permeability (Papp of rhodamine 123 from a water solution across the monolayer was $2.45{\times}10^{-6}$ cm/s for $A{\leftrightarrow}B$ (apical to basal) and $14.0{\times}10^{-6}$ cm/s for $B{\leftrightarrow}A$ (basal to apical) directions, consistent with the fact that rhodamine 123 is one of the P-gp substrates. The transport of rhodamine 123 from the liposomal dosage form was much lower for both directions compared to the solution of rhodamine 123. The transport of rhodamine 123 across the rat intestine was also significantly decreased for both directions, I.e., influx and efflux, by the liposomal incorporation of the compound. The transport of rhodamine 123 across the Peyer's patch was substantially reduced by liposomal incorporation. No difference was found in the transport between the Peyer's patch and non-Peyer's patch. These observations suggest that the contribution of transport via Peyer's patches in the uptake of liposomes may be minimal, especially for rapidly absorbed compounds like rhodamine 123. Therefore, the increased absorption of P-gp substrates does not appear to be feasible by incorporating the compounds in liposomes, due to negligible involvement of Peyer's patches in the uptake of particulate dosage forms like liposomes. Liposomes may rather represent a sustained release dosage form of incorporated compounds.

옥덩굴 에탄올 추출물의 당 대사 및 인슐린 민감성 개선효과 (Caulerpa okamurae ethanol extract improves the glucose metabolism and insulin sensitivity in vitro and in vivo)

  • 박철민;타쿠리랙스미센;류동영
    • Journal of Applied Biological Chemistry
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    • 제64권1호
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    • pp.89-96
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    • 2021
  • 이 연구의 목적은 Caulerpa okamurae 에탄올 추출물(COE)이 제2형 당뇨병 치료의 약물 표적 중 하나인 당 대사 및 인슐린 민감성에 미치는 영향을 평가하는 것이다. COE는 in vitro 실험에서 단백질 티로신 포스타제 1B (PTP1B)와 디펩티딜 펩티데이즈-IV (DPP-IV) 효소 활성을 유의하게 억제시켰다. 또한, COE는 3T3-L1 지방세포와 제브라피쉬에서 당 흡수, 인슐린 수용체 기질(IRS-1) 및 당 수송체(GLUT4) 단백의 발현을 대조군에 비해 유의하게 향상시켰다. L6 근육세포의 덱사메타손(dexamethasone)으로 유도된 인슐린 저항성 모델에서도 COE는 인슐린 신호전달 및 당 흡수 단백의 발현을 효과적으로 증가시켰다. 더불어 인슐린 저항성 지표로 알려진 IRS-1 Ser307의 인산화 활성도 COE 첨가에 의해 유의하게 억제되었다. 그러나 COE는 췌장 베타세포의 인슐린 분비에는 아무런 영향을 미치지 않았다. 결론적으로 COE는 인슐린 표적세포와 제브라피쉬에서 인슐린 신호전달과 당 수송체 GLUT4 단백 발현의 조절을 통해 당 대사 및 인슐린 민감성을 개선시키는 것으로 밝혀졌다.

순환식 수경재배에 적합한 방울토마토 '꼬꼬' 배양액 개발 (Development of Optimal Nutrient Solution of Cherry Tomato (Lycopersicon esculentum Mill. 'KoKo') in a Closed Soilless Culture System)

  • 유성오;최기영;전경수;배종향
    • 생물환경조절학회지
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    • 제15권1호
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    • pp.69-77
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    • 2006
  • The experiment was conducted to investigate the nutrition absorption pattern in the growth stage and develope the optimal nutrient solution hydroponically grown the cherry tomato 'Koko' in closed substrate culture system with the nutrient solution of National Horticultural Research Station in Japan into 1/2S, 1S, and 2S. When plant was grown in 1/2S, the growth and yield were high and the pH and EC in the root zone were stable. Suitable composition of nutrient solution for cherry tomato was $NO_3-N\;6.8,\;PO_4-P\;2.7,\;K 3.2,\;Ca\;3.6\;and\;Mg\;1.1\;me\;L^{-1}$ in the early growth stage, $NO_3-N\;7.3,\;PO_4-P\;2.2,\;K\;3.7,\;Ca\;3.6;and\;Mg\;1.1\;me\;L^{-1}$ in the late growth stage by calculating a rate of nutrient and water uptake. To estimate the suitability for the nutrient solution in a development of cherry tomato developed by Wongkwang university in Korea (WU), plant was grown in perlite substrate supplied with different solution and strengths(S) by research station for greenhouse vegetable and floriculture in the Netherlands (Proefstation voor tuinbouw onder glas th Mssldwijk; PTG) of 1/2S, 1S, and 2S, respectively. The growth was good at the PTG and WU 2S in the early stage and the PTG of 1S and WU of 1S and 2S in the late stage. The highest yield of cherry tomato obtained in the WU of 2S. pH and EC in root zone of WU of 2S were stable during the early and late growth stage. Therefore when cherry tomato plant was grown in WU of 2S of EC $1.6{\sim}2.0\;dS\;m^{-1}$in the nutrient solution, not only stable growth and yield but also fertilizer reduction can be obtained than that of PTG.

Telmisartan increases hepatic glucose production via protein kinase C ζ-dependent insulin receptor substrate-1 phosphorylation in HepG2 cells and mouse liver

  • Cho, Kae Won;Cho, Du-Hyong
    • Journal of Yeungnam Medical Science
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    • 제36권1호
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    • pp.26-35
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    • 2019
  • Background: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice. Methods: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase ${\alpha}$ ($G6Pase-{\alpha}$), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ${\zeta}$ ($PKC{\zeta}$) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice. Results: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a $40{\mu}M$ concentration without a change in $G6Pase-{\alpha}$ expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 ($p-IRS-1-Ser^{302}$) and decreased $p-IRS-1-Tyr^{632}$ dose-dependently. Telmisartan dose-dependently increased $p-PKC{\zeta}-Thr^{410}$ which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative $PKC{\zeta}$ significantly attenuated telmisartan-induced HGP and $p-IRS-1-Ser^{302}$ and -inhibited $p-IRS-1-Tyr^{632}$. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased $p-IRS-1-Ser^{302}$ and decreased $p-IRS-1-Tyr^{632}$, which was accompanied by an increase in $p-PKC{\zeta}-Thr^{410}$. Conclusion: These results suggest that telmisartan increases HGP by inducing $p-PKC{\zeta}-Thr^{410}$ that increases $p-IRS-1-Ser^{302}$ and decreases $p-IRS-1-Tyr^{632}$ in a $PPAR{\gamma}$-independent manner

Effects of Phloretin, Cytochalasin B, and D-Fructose on 2-deoxy-D-Glucose Transport of the Glucose Transport System Present in Spodoptera frugiperda Clone 21-AE Cells

  • Lee Chong-Kee
    • 대한의생명과학회지
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    • 제12권1호
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    • pp.17-22
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    • 2006
  • The baculovirus expression system is a powerful method for producing large amounts of the human erythrocyte-type glucose transport protein, heterologously. Characterization of the expressed protein is expected to show its ability to transport sugars directly. To achieve this, it is a prerequisite to know the properties of the endogenous sugar transport system in Spodoptera frugiperda Clone 21 (Sf21) cells, which are commonly employed as a host permissive cell line to support the baculovirus replication. The Sf21 cells can grow well on TC-100 medium that contains 0.1% D-glucose as the major carbon source, strongly suggesting the presence of endogenous glucose transport system. However, unlike the human glucose transport protein that has a broad substrate and inhibitor specificity, very little is known about the nature of the endogenous sugar transport system in Sf21 cells. In order to characterize further the inhibitor recognition properties of the Sf21 cell transporter, the ability of phloretin, cytochalasin B and D-fructose to inhibit 2-deoxy-D-glucose (2dGlc) transport was examined by measuring inhibition constants $(K_i)$. The $K_i's$ for reversible inhibitors were determined from plots of uptake versus inhibitor concentration. The 2dGlc transport in the Sf21 cells was very potently inhibited by phloretin, the aglucone of phlorizin with a $K_i$ similar to the value of about $2{\mu}M$ reported for inhibition of glucose transport in human erythrocytes. However, the Sf21 cell transport system was found to differ from the human transport protein in being much less sensitive to inhibition by cytochalasin B (apparent $K_i$ approximately $10\;{\mu}M$). In contrast, It is reported that the inhibitor binds the human erythrocyte counterpart with a $K_d$ of approximately $0.12\;{\mu}M$. Interestingly, the Sf21 glucose transport system also appeared to have high affinity for D-fructose with a $K_i$ of approximately 5mM, contrasting the reported $K_m$ of the human erythrocyte transport protein for the ketose of 1.5M.

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Plant Uptake of Heavy Metals in Andong Serpentine Soil

  • Kim, Jeong-Myeong;Yang, Keum-Chul;Choi, Sang-Kyoo;Yeon, Myung-Hun;Shin, Jin-Ho;Shim, Jae-Kuk
    • 환경생물
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    • 제24권4호
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    • pp.408-415
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    • 2006
  • Serpentines soil have high values of magnesium and low values of calcium, and are usually deficient in N and P, but rich in iron, Ni, silicates. We investigated serpentine soil properties and measured the content of nutrient elements and heavy metals in shoots and root of plant species which were in common at serpentine and non-serpentine areas in Andong, Korea. The soils showed higher pH value above 6.9. The contents of Ni, Cr, Fe and Mg of serpentine soils exhibited 77, 27, 5.5 and 12.5 times more than in non-serpentine soils, respectively. The content of Na was almost same but K was two times higher in non-serpentine soil, compared with serpentine soil. The contents of nutrient element such as K, Ca, Na and P in serpentine plants did not show conspicuous differences with non-serpentine plants. On the other hand, the concentrations of Ni, Cr, Fe, Mg and Mg/Ca were very high in plant on serpentine area. The all plant species collected at the serpentine site were bodenvag plants, which are not restricted to a specific type of substrate. By the plant species and parts of plant tissues, the absorption levels and patterns showed high variation and were species-specific. Carex lanceolata, Lysimachia clethroides and Cynanchum paniculatum contained much chromium and Eupatorium chinense and C. paniculatum exhibited high contents of Ni. In leaf tissue, C. lanceolata, Rubus parvifolius, Festuca ovina, Quercus serrata, and L. clethroides took comparatively large amount of Cr in serpentine area. E. chinense contained large amount of Ni, Cr and Fe in a leaf tissue. The stem of Galium verum, Juniperus rigida included high amount of Cr, Ni and Fe. And C. paniculatum absorbed large amount of Ni and Cr in the stem.

Photolithographic Fabrication of Poly(Ethylene Glycol) Microstructures for Hydrogel-based Microreactors and Spatially Addressed Microarrays

  • Baek, Taek-Jin;Kim, Nam-Hyun;Choo, Jae-Bum;Lee, Eun-Kyu;Seong, Gi-Hun
    • Journal of Microbiology and Biotechnology
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    • 제17권11호
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    • pp.1826-1832
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    • 2007
  • We describe the fabrication of poly(ethylene glycol) diacrylate (PEG-DA) hydrogel microstructures with a high aspect ratio and the use of hydrogel microstructures containing the enzyme ${\beta}$-galactosidase (${\beta}$-Gal) or glucose oxidase (GOx)/horseradish peroxidase (HRP) as biosensing components for the simultaneous detection of multiple analytes. The diameters of the hydrogel microstructures were almost the same at the top and at the bottom, indicating that no differential curing occurred through the thickness of the hydrogel microstructure. Using the hydrogel microstructures as microreactors, ${\beta}$-Gal or GOx/HRP was trapped in the hydrogel array, and the time-dependent fluorescence intensities of the hydrogel array were investigated to determine the dynamic uptake of substrates into the PEG-DA hydrogel. The time required to reach steady-state fluorescence by glucose diffusing into the hydrogel and its enzymatic reactions with GOx and HRP was half the time required for resorufin ${\beta}$-D-galactopyranoside (RGB) when used as the substrate for ${\beta}$-Gal. Spatially addressed hydrogel microarrays containing different enzymes were micropatterned for the simultaneous detection of multiple analytes, and glucose and RGB solutions were incubated as substrates. These results indicate that there was no cross-talk between the ${\beta}$-Gal-immobilizing hydrogel micropatches and the GOx/HRP-immobilizing micropatches.

금속 입자 크기가 토양 미생물 군집과 메밀에 미치는 영향 (Effects of Size of Metal Particles on Soil Microbial Community and Buck Wheat)

  • 김성현;김정은;곽영지;김연지;이인숙
    • 한국환경과학회지
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    • 제20권4호
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    • pp.457-463
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    • 2011
  • This study was carried out to compare the toxicity of nano and micrometer particles with Cu and Zn on soil microbial community and metal uptake of buck wheat. In microcosm system, soil was incubated for 14 days after soil aliquots were artificially contaminated with 1,000 mg/kg Cu, Zn nano and micro particles, respectively. After then, buck wheat was planted in incubating soils and non incubating soils. After 14 days, we compared bioaccumulation of metal, and microbial carbon substrate utilization patterns between incubating soils and non-incubating soils. The enrichment factor (EF) values of incubating samples were greater than non-incubating soils. Dehydrogenase activity had been inhibited by Cu and Zn nanoparticles in non-incubating soil, as well as it had been inhibited by Zn micro particles in incubating soils. Results of biolog test, it was not significant different between nano particles and micro particles. It cannot be generalized that nanoparticles of metal are always more toxic to soil microbial activity and diversity than micrometer-sized particles and the toxicity needs to be assessed on a case-by-case basis.

인체 갑상세포의 대사조절에 의한 프로 유로카이나제의 생산 (Metabolic Control of Maintenance for the Production of pro-Urokinase from Human Thyroid cells)

  • 강재구;최석규;이현용
    • 한국미생물·생명공학회지
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    • 제18권4호
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    • pp.401-405
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    • 1990
  • 5 혈청을 포함한 DMEM 배지에 갑상세포주 579를 연속배양하여 약 $5.7 \times 10^{-8}$g/h /cell에 해당하는 pro-UK의 비생산속도를 얻을 수 있었다. 또한 배지의 이동속도가 증가할 수록 glutamine의 소비속도가 증가하는 반면 ammonia 생산속도는 일정하게 유지되는, glutamine의 완전동화에의한 물질생산증가 현상을 나타냈다. 5mM의 glucose와 2mM의 glutamine, 포화용존 공기의 10에 해당하는 용존산소 및 pH 6.2의 maintenance 생육 조건하에서 약 15일간 유지시켜, $12\times 10^{-8}$g of pro-UK/h/cell의 최대 비생산속도와 0.226mg/g of glucose의 생산수율을 얻었으며, 이는 10ml/min의 배지 이동속도를 유지하는 연속배양 조건에서 매일 0.223mg의 pro-KU를 생산할 수 있을을 의미한다.

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