Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons.The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in mus...Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons.The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in muscle to chronic cold exposure via Min pig models(cold adaptation)and Yorkshire pig models(non-cold adaptation).Furthermore,this study explored the beneficial effects of glucose supplementation on small intestinal amino acid transport and amino acid pool in muscle of cold-exposed Yorkshire pigs.Min pigs(Exp.1)and Yorkshire pigs(Exp.2)were divided into a control group(17℃,n=6)and chronic cold exposure group(7℃,n=6),respectively.Twelve Yorkshire pigs(Exp.3)were divided into a cold control group and cold glucose supplementation group(8℃).The results showed that chronic cold exposure inhibited peptide transporter protein 1(PepT1)and excitatory amino acid transporter 3(EAAT3)expression in ileal mucosa and cationic amino acid transporter-1(CAT-1)in the jejunal mucosa of Yorkshire pigs(P<0.05).In contrast,CAT-1,PepT1 and EAAT3 expression was enhanced in the duodenal mucosa of Min pigs(P<0.05).Branched amino acids(BCAA)in the muscle of Yorkshire pigs were consumed by chronic cold exposure,accompanied by increased muscle RING-finger protein-1(MuRF1)and muscle atrophy F-box(atrogin-1)expression(P<0.05).More importantly,reduced concentrations of dystrophin were detected in the muscle of Yorkshire pigs(P<0.05).However,glycine concentration in the muscle of Min pigs was raised(P<0.05).In the absence of interaction between chronic cold exposure and glucose supplementation,glucose supplementation improved CAT-1 expression in the jejunal mucosa and PepT1 expression in the ileal mucosa of cold-exposed Yorkshire pigs(P<0.05).It also improved BCAA and inhibited MuRF1 and atrogin-1 expression in muscle(P<0.05).Moreover,dystrophin concentration was improved by glucose supplementation(P<0.05).In summary,chronic cold exposure inhibits amino acid absorption in the small intestine,depletes BCAA and promotes protein degradation in muscle.Glucose supplementation ameliorates the negative effects of chronic cold exposure on amino acid transport and the amino acid pool in muscle.展开更多
Background The delivery of glucose from the blood to the brain involves its passage across the endothelial cells of the blood-brain barrier （BBB）, which is mediated by the facilitative glucose transporter protein 1 ...Background The delivery of glucose from the blood to the brain involves its passage across the endothelial cells of the blood-brain barrier （BBB）, which is mediated by the facilitative glucose transporter protein 1 （GLUT1）, end then across the neural cell membranes, which is mediated by GLUT3. This study aimed to evaluate the dynamic influence of hyperglycemia on the expression of these GLUTs by measuring their expression in the brain at different blood glucose levels in e rat model of diabetes. This might help to determine the proper blood glucose threshold level in the treatment of diabetic apoplexy. Methods Diabetes mellitus was induced with streptozotocin （STZ） in 30 rats. The rats were randomly divided into 3 groups： diabetic group without blood glucose control （group DM1）, diabetic rats treated with low dose insulin （group DM2） end diabetic rats treated with high dose insulin （group DM3）. The mRNA end protein levels of GLUT1 end GLUT3 were essayed by reverse trenscriptese-polymerese chain reaction （RT-PCR） end immunohistochemistry, respectively. Results Compared with normal control rats, the G/UT1 mRNA was reduced by 46.08%, 29.80%, 19.22% （P〈0.01） in DM1, DM2, end DM3 group, respectively; end the GLUT3 mRNA was reduced by 75.00%, 46.75%, end 17.89% （P〈0.01） in DM1, DM2, end DM3 group, respectively. The abundance of GLUT1 end GLUT3 proteins had negative correlation with the blood glucose level （P〈0.01）. The density of microvessels in the brain of diabetic rats did not change significantly compared with normal rats. Conclusions Chronic hyperglycemia downreguletes G/UT1 end GLUT3 expression at both mRNA end protein levels in the rat brain, which is not due to the decrease of the density of microvessels. The downreguletion of G/UT1 end GLUT3 expression might be the adaptive reaction of the body to prevent excessive glucose entering the cell that may lead to cell damage.展开更多
近年来,随着对肿瘤生物学研究的不断深入,人们对复杂的肿瘤代谢重编程更新、更全面的认识。葡萄糖转运蛋白1(glucose transport protein-1,GLUT-1)在不同肿瘤细胞的质膜上有不同程度的过度表达,过表达的GLUT-1会使肿瘤细胞摄入更多的葡...近年来,随着对肿瘤生物学研究的不断深入,人们对复杂的肿瘤代谢重编程更新、更全面的认识。葡萄糖转运蛋白1(glucose transport protein-1,GLUT-1)在不同肿瘤细胞的质膜上有不同程度的过度表达,过表达的GLUT-1会使肿瘤细胞摄入更多的葡萄糖以重编程细胞的代谢模式,。同时,对肿瘤微环境的改变有着重要的影响。并且,在肿瘤中GLUT-1的调节是近年来关注的重点,目前,已报道的上游调控因子主要有PTEN基因编码的蛋白质(phosphatase and tension homolog deleted on chromosome ten,PTEN)、缺氧诱导因子(hypoxia inducible factor,HIF),GLUT-1还会通过影响p53和细胞致瘤基因(cellular-myelocytomatosis viral oncogene,c-Myc)通路等在肿瘤的发生与发展中发挥着重要的作用。本文主要综述GLUT-1的结构与功能、在肿瘤代谢重编程中通过转运不同底物对肿瘤的影响、GLUT-1的调节和目前针对GLUT-1的治疗等。同时,阐述了GLUT-1与肿瘤代谢重编程的研究现状,分析了当前存在的问题,旨在为抗肿瘤机制研究以及恶性肿瘤靶向治疗研究提供参考。展开更多
Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in hig...Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.展开更多
目的:探讨乳源活性肽β-酪啡肽-7(β-Casomorphin-7,β-CM7)应用于食品时对葡萄糖吸收的影响及其作用机制.方法:选用健康成年SD大鼠,分为对照组(0mol/Lβ-CM7),L低剂量组、M中剂量组、H高剂量组(终浓度分别为7.5×10-7,7.5×10-...目的:探讨乳源活性肽β-酪啡肽-7(β-Casomorphin-7,β-CM7)应用于食品时对葡萄糖吸收的影响及其作用机制.方法:选用健康成年SD大鼠,分为对照组(0mol/Lβ-CM7),L低剂量组、M中剂量组、H高剂量组(终浓度分别为7.5×10-7,7.5×10-6,7.5×10-5mol/L).利用翻转离体小肠囊模型进行实验:(1)葡萄糖氧化酶法测定翻转后小肠内液葡萄糖含量;(2)比色法测定小肠黏膜Na+-K+-ATP酶活力;(3)荧光定量PCR法分析小肠黏膜组织中钠葡萄糖共转运载体(SGLT-1)和葡萄糖协助扩散转运载体(GLUT-2) mRNA的表达.结果:在离体环境下β-CM7在7.5×10-7-7.5×10-5mol/L浓度下对葡萄糖的吸收均有一定的抑制作用(1.09mol/L,1.24mol/L,1.12mol/L vs 1.74mol/L,P=0.01,0.04,0.02),能够降低Na+-K+-ATP酶活力(85.73,112.06,109.68 vs 114.93,P=0.004,0.73,0.54);荧光定量PCR结果发现:与对照组相比,β-CM7能够显著降低SGLT-1及GLUT-2 mRNA水平(0.46,0.58,0.77 vs 1.11,P=0.20,0.05,0.02;0.50,0.66,0.85 vs 1.14,P=0.30,0.14,0.03).结论:β-CM7可以通过降低Na+-K+-ATP酶活力及下调SGLT-1、GLUT-2 mRNA水平,减少大鼠小肠对葡萄糖的吸收.展开更多
基金This work was supported by the National Key R&D Program of China(2021YFD1300403)the Major Program of Heilongjiang Province of China(2021ZX12B08-02).
文摘Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons.The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in muscle to chronic cold exposure via Min pig models(cold adaptation)and Yorkshire pig models(non-cold adaptation).Furthermore,this study explored the beneficial effects of glucose supplementation on small intestinal amino acid transport and amino acid pool in muscle of cold-exposed Yorkshire pigs.Min pigs(Exp.1)and Yorkshire pigs(Exp.2)were divided into a control group(17℃,n=6)and chronic cold exposure group(7℃,n=6),respectively.Twelve Yorkshire pigs(Exp.3)were divided into a cold control group and cold glucose supplementation group(8℃).The results showed that chronic cold exposure inhibited peptide transporter protein 1(PepT1)and excitatory amino acid transporter 3(EAAT3)expression in ileal mucosa and cationic amino acid transporter-1(CAT-1)in the jejunal mucosa of Yorkshire pigs(P<0.05).In contrast,CAT-1,PepT1 and EAAT3 expression was enhanced in the duodenal mucosa of Min pigs(P<0.05).Branched amino acids(BCAA)in the muscle of Yorkshire pigs were consumed by chronic cold exposure,accompanied by increased muscle RING-finger protein-1(MuRF1)and muscle atrophy F-box(atrogin-1)expression(P<0.05).More importantly,reduced concentrations of dystrophin were detected in the muscle of Yorkshire pigs(P<0.05).However,glycine concentration in the muscle of Min pigs was raised(P<0.05).In the absence of interaction between chronic cold exposure and glucose supplementation,glucose supplementation improved CAT-1 expression in the jejunal mucosa and PepT1 expression in the ileal mucosa of cold-exposed Yorkshire pigs(P<0.05).It also improved BCAA and inhibited MuRF1 and atrogin-1 expression in muscle(P<0.05).Moreover,dystrophin concentration was improved by glucose supplementation(P<0.05).In summary,chronic cold exposure inhibits amino acid absorption in the small intestine,depletes BCAA and promotes protein degradation in muscle.Glucose supplementation ameliorates the negative effects of chronic cold exposure on amino acid transport and the amino acid pool in muscle.
文摘Background The delivery of glucose from the blood to the brain involves its passage across the endothelial cells of the blood-brain barrier （BBB）, which is mediated by the facilitative glucose transporter protein 1 （GLUT1）, end then across the neural cell membranes, which is mediated by GLUT3. This study aimed to evaluate the dynamic influence of hyperglycemia on the expression of these GLUTs by measuring their expression in the brain at different blood glucose levels in e rat model of diabetes. This might help to determine the proper blood glucose threshold level in the treatment of diabetic apoplexy. Methods Diabetes mellitus was induced with streptozotocin （STZ） in 30 rats. The rats were randomly divided into 3 groups： diabetic group without blood glucose control （group DM1）, diabetic rats treated with low dose insulin （group DM2） end diabetic rats treated with high dose insulin （group DM3）. The mRNA end protein levels of GLUT1 end GLUT3 were essayed by reverse trenscriptese-polymerese chain reaction （RT-PCR） end immunohistochemistry, respectively. Results Compared with normal control rats, the G/UT1 mRNA was reduced by 46.08%, 29.80%, 19.22% （P〈0.01） in DM1, DM2, end DM3 group, respectively; end the GLUT3 mRNA was reduced by 75.00%, 46.75%, end 17.89% （P〈0.01） in DM1, DM2, end DM3 group, respectively. The abundance of GLUT1 end GLUT3 proteins had negative correlation with the blood glucose level （P〈0.01）. The density of microvessels in the brain of diabetic rats did not change significantly compared with normal rats. Conclusions Chronic hyperglycemia downreguletes G/UT1 end GLUT3 expression at both mRNA end protein levels in the rat brain, which is not due to the decrease of the density of microvessels. The downreguletion of G/UT1 end GLUT3 expression might be the adaptive reaction of the body to prevent excessive glucose entering the cell that may lead to cell damage.
文摘目的 研究补肾健脾方改善胎鼠宫内发育迟缓(intrauterine growth retardation,IUGR)的作用及分子机制。方法 将妊娠SD大鼠随机分为对照组、模型组、低剂量组、中剂量组、高剂量组,对照组给予常规饲料喂养,后4组采用低蛋白饲料喂养的方式建立IUGR模型;对照组和模型组给予生理盐水灌胃,每日1次,低剂量组、中剂量组、高剂量组分别给予1/2等效剂量、等效剂量、2倍等效剂量的补肾健脾方灌胃,每日1次,各组在妊娠第1~18天连续给药,妊娠第18天时剖宫产取胎盘及胎鼠,测量胎鼠的体质量、体长、胰岛素抵抗指数(homeostatic model assessment of insulin resistance,HOMA-IR)、胰岛β细胞功能指数(homeostasis model assessment-β,HOMA-β)以及胎盘、胎鼠骨骼肌中磷酸化磷脂酰肌醇3激酶(phosphoinositide 3-kinase,p-PI3K)、磷酸化蛋白激酶B(phosphorylation protein kinase B,p-AKT)、葡萄糖转运蛋白1(glucose transporter 1,GLUT1)的表达水平。结果 模型组胎鼠的体质量、体长、HOMA-β以及胎盘、胎鼠骨骼肌中p-PI3K、p-AKT、GLUT1的表达水平低于对照组,HOMA-IR高于对照组(P<0.05);低剂量组、中剂量组、高剂量组胎鼠的体质量、体长、HOMA-β以及胎盘、胎鼠骨骼肌中p-PI3K、p-AKT、GLUT1的表达水平高于模型组,HOMA-IR低于模型组(P<0.05);高剂量组的各项测量指标与对照组比较,差异无统计学意义(P>0.05)。结论 补肾健脾方可改善胎鼠IUGR及胰岛素抵抗,激活胎盘、骨骼肌中PI3K/AKT/GLUT途径是补肾健脾方发挥上述改善作用可能发生的分子机制。
文摘近年来,随着对肿瘤生物学研究的不断深入,人们对复杂的肿瘤代谢重编程更新、更全面的认识。葡萄糖转运蛋白1(glucose transport protein-1,GLUT-1)在不同肿瘤细胞的质膜上有不同程度的过度表达,过表达的GLUT-1会使肿瘤细胞摄入更多的葡萄糖以重编程细胞的代谢模式,。同时,对肿瘤微环境的改变有着重要的影响。并且,在肿瘤中GLUT-1的调节是近年来关注的重点,目前,已报道的上游调控因子主要有PTEN基因编码的蛋白质(phosphatase and tension homolog deleted on chromosome ten,PTEN)、缺氧诱导因子(hypoxia inducible factor,HIF),GLUT-1还会通过影响p53和细胞致瘤基因(cellular-myelocytomatosis viral oncogene,c-Myc)通路等在肿瘤的发生与发展中发挥着重要的作用。本文主要综述GLUT-1的结构与功能、在肿瘤代谢重编程中通过转运不同底物对肿瘤的影响、GLUT-1的调节和目前针对GLUT-1的治疗等。同时,阐述了GLUT-1与肿瘤代谢重编程的研究现状,分析了当前存在的问题,旨在为抗肿瘤机制研究以及恶性肿瘤靶向治疗研究提供参考。
基金supported by National Natural Science Foundation of China(32072212)Multi-Year Research Grant of University of Macao(MYRG2018-00169-ICMS)+5 种基金Science and Technology Development Fund of Macao(FDCT)(0098/2020/A)MICINN supporting the Ramón y Cajal grant for M.A.Prieto(RYC-201722891)Jianbo Xiao(RYC2020-030365-I)Xunta de Galicia supporting the Axudas Conecta Peme,the IN852A 2018/58 Neuro Food Project,the program EXCELENCIA-ED431F 2020/12the pre-doctoral grants of P.García-Oliveira(ED481A-2019/295)to Ibero-American Program on Science and Technology(CYTED-AQUA-CIBUS,P317RT0003).
文摘Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.
文摘目的:探讨乳源活性肽β-酪啡肽-7(β-Casomorphin-7,β-CM7)应用于食品时对葡萄糖吸收的影响及其作用机制.方法:选用健康成年SD大鼠,分为对照组(0mol/Lβ-CM7),L低剂量组、M中剂量组、H高剂量组(终浓度分别为7.5×10-7,7.5×10-6,7.5×10-5mol/L).利用翻转离体小肠囊模型进行实验:(1)葡萄糖氧化酶法测定翻转后小肠内液葡萄糖含量;(2)比色法测定小肠黏膜Na+-K+-ATP酶活力;(3)荧光定量PCR法分析小肠黏膜组织中钠葡萄糖共转运载体(SGLT-1)和葡萄糖协助扩散转运载体(GLUT-2) mRNA的表达.结果:在离体环境下β-CM7在7.5×10-7-7.5×10-5mol/L浓度下对葡萄糖的吸收均有一定的抑制作用(1.09mol/L,1.24mol/L,1.12mol/L vs 1.74mol/L,P=0.01,0.04,0.02),能够降低Na+-K+-ATP酶活力(85.73,112.06,109.68 vs 114.93,P=0.004,0.73,0.54);荧光定量PCR结果发现:与对照组相比,β-CM7能够显著降低SGLT-1及GLUT-2 mRNA水平(0.46,0.58,0.77 vs 1.11,P=0.20,0.05,0.02;0.50,0.66,0.85 vs 1.14,P=0.30,0.14,0.03).结论:β-CM7可以通过降低Na+-K+-ATP酶活力及下调SGLT-1、GLUT-2 mRNA水平,减少大鼠小肠对葡萄糖的吸收.
