Abstract:Here we have investigated the inhibitory properties of green tea catechins on the Plasmodium falciparum hexose transporter (PfHT), the Babesia bovis hexose transporter 1 (BboHT1) and the mammalian facilitative glucose transporters, GLUT1 and GLUT5, expressed in Xenopus laevis oocytes. (−)-Epicatechin-gallate (ECG) and (−)-epigallocatechin-gallate (EGCG) inhibited d-glucose transport by GLUT1 and PfHT, and d-fructose transport by GLUT5, with apparent Ki values between 45 and 117 μM. BboHT1 was more potently inh… Show more
“…laevis oocytes. Thus, with the hxt
0
GLUT5 system IC 50 value for fructose uptake inhibition by (−)-epicatechin-gallate (ECG) was comparable to the K i value previously reported 18 . Also the IC 50 for MSNBA inhibition of fructose uptake by hxt
0
GLUT5 is comparable to that determined in human breast carcinoma MCF-7 cells and ~10-fold lower than that determined in GLUT5 proteoliposomes 20 , making the yeast system superior to GLUT5 proteoliposomes and comparable to human cell lines systems in assessing GLUT5 inhibition.…”
Section: Discussionsupporting
confidence: 86%
“…Although there is a slight variation between the mutants, their kinetic parameters are similar to those determined in MCF-7 cells 17, 20 or X . laevis oocytes 18 , indicating that the mutations do not have a major influence on the transport mechanism. Reported K M values for human GLUT5 fructose uptake vary between 6 and 15 mM 3, 17, 40 .Figure 4Transport kinetics and inhibition of GLUT5 mutants in hxt
0 cells.…”
Human GLUT5 is a fructose-specific transporter in the glucose transporter family (GLUT, SLC2 gene family). Its substrate-specificity and tissue-specific expression make it a promising target for treatment of diabetes, metabolic syndrome and cancer, but few GLUT5 inhibitors are known. To identify and characterize potential GLUT5 ligands, we developed a whole-cell system based on a yeast strain deficient in fructose uptake, in which GLUT5 transport activity is associated with cell growth in fructose-based media or assayed by fructose uptake in whole cells. The former method is convenient for high-throughput screening of potential GLUT5 inhibitors and activators, while the latter enables detailed kinetic characterization of identified GLUT5 ligands. We show that functional expression of GLUT5 in yeast requires mutations at specific positions of the transporter sequence. The mutated proteins exhibit kinetic properties similar to the wild-type transporter and are inhibited by established GLUT5 inhibitors N-[4-(methylsulfonyl)-2-nitrophenyl]-1,3-benzodioxol-5-amine (MSNBA) and (−)-epicatechin-gallate (ECG). Thus, this system has the potential to greatly accelerate the discovery of compounds that modulate the fructose transport activity of GLUT5.
“…laevis oocytes. Thus, with the hxt
0
GLUT5 system IC 50 value for fructose uptake inhibition by (−)-epicatechin-gallate (ECG) was comparable to the K i value previously reported 18 . Also the IC 50 for MSNBA inhibition of fructose uptake by hxt
0
GLUT5 is comparable to that determined in human breast carcinoma MCF-7 cells and ~10-fold lower than that determined in GLUT5 proteoliposomes 20 , making the yeast system superior to GLUT5 proteoliposomes and comparable to human cell lines systems in assessing GLUT5 inhibition.…”
Section: Discussionsupporting
confidence: 86%
“…Although there is a slight variation between the mutants, their kinetic parameters are similar to those determined in MCF-7 cells 17, 20 or X . laevis oocytes 18 , indicating that the mutations do not have a major influence on the transport mechanism. Reported K M values for human GLUT5 fructose uptake vary between 6 and 15 mM 3, 17, 40 .Figure 4Transport kinetics and inhibition of GLUT5 mutants in hxt
0 cells.…”
Human GLUT5 is a fructose-specific transporter in the glucose transporter family (GLUT, SLC2 gene family). Its substrate-specificity and tissue-specific expression make it a promising target for treatment of diabetes, metabolic syndrome and cancer, but few GLUT5 inhibitors are known. To identify and characterize potential GLUT5 ligands, we developed a whole-cell system based on a yeast strain deficient in fructose uptake, in which GLUT5 transport activity is associated with cell growth in fructose-based media or assayed by fructose uptake in whole cells. The former method is convenient for high-throughput screening of potential GLUT5 inhibitors and activators, while the latter enables detailed kinetic characterization of identified GLUT5 ligands. We show that functional expression of GLUT5 in yeast requires mutations at specific positions of the transporter sequence. The mutated proteins exhibit kinetic properties similar to the wild-type transporter and are inhibited by established GLUT5 inhibitors N-[4-(methylsulfonyl)-2-nitrophenyl]-1,3-benzodioxol-5-amine (MSNBA) and (−)-epicatechin-gallate (ECG). Thus, this system has the potential to greatly accelerate the discovery of compounds that modulate the fructose transport activity of GLUT5.
“…The growth‐inhibiting effect of flavonoids has already been demonstrated for Plasmodium falciparum, belonging to the same phylum as A. bombi (i.e., Apicomplexa; Slavic et al. ). Although the presence of secondary metabolites is a very strong hypothesis for explaining the lower prevalence of a subset of parasite species detected in Bombus pascuorum population from invaded sites, additional experimental assays (e.g., test on the biological activities of the secondary metabolites) are needed to fully validate this hypothesis and to understand the associated mechanisms.…”
Section: Discussionmentioning
confidence: 94%
“…In this study, the multidirectional biological activity of I. glandulifera (especially antimicrobial properties due to flavonoids occurrence in pollen) coupled with the active foraging of bumble bee workers on the invasive plant could explain the lower Apicystis bombi prevalence in invaded sites (Appendix S5: Table S4). The growth-inhibiting effect of flavonoids has already been demonstrated for Plasmodium falciparum, belonging to the same phylum as A. bombi (i.e., Apicomplexa; Slavic et al 2009). Although the presence of secondary metabolites is a very strong hypothesis for explaining the lower prevalence of a subset of parasite species detected in Bombus pascuorum population from invaded sites, additional experimental assays (e.g., test on the biological activities of the secondary metabolites) are needed to fully validate this hypothesis and to understand the associated mechanisms.…”
Section: Parasite Prevalence and Impact Of Impatiens Glanduliferamentioning
While many bee species are experiencing population declines, some host plant generalist bees remain common in Europe, partly because they seem able to shift to new resources. However, foraging on a new alternative plant, such as an invasive species, can modify diet quality and have a potentially detrimental effect on bee health. Herein, we investigated whether the spread of the invasive plant Impatiens glandulifera affects Bombus pascuorum population regarding parasite prevalence, genetic structure, and nest density in Belgium. While no difference in bumble bee genetic structure was detected between invaded and uninvaded sites, we show that I. glandulifera occurrence was significantly correlated with a decrease in the prevalence of Apicystis bombi but not the prevalence of three other parasite species (i.e., Crithidia bombi, Nosema bombi, Nosema ceranae, and Nosema sp.). Regarding our investigations, this effect was likely not due to variation in local bumble bee population fitness before I. glandulifera flowering, nor to the relative abundance of other pollinators such as Apis mellifera, but the unique chemical composition (i.e., polyphenol rich) of the pollen of I. glandulifera remained as an interesting hypothesis. Whereas B. pascuorum queens probably colonize all the potential nesting sites in an area, invaded by I. glandulifera or not, the abundance of polyphenol ampelopsin in pollen from I. glandulifera pollen might reduce local parasite prevalence. Our field study confirms that bumble bee parasite prevalence is potentially related to the particular chemical composition of collected pollen. Plant traits such as secondary metabolite occurrence could play a key role in the health and conservation of bumble bees.
“…This action of EGCG on GLUTs may be related to its gallate moiety, because ECG and genistein also have a blocking effect toward GLUTs, and ECG is the more potent 31, 39. The mechanism of EGCG to inhibit cellular glucose uptake may be either blockade of insulin signaling or direct competition with glucose for GLUTs 16, 43. We found that insulin-induced Ser473 phosphorylation of protein kinase B remained unchanged in the presence of EGCG in hepatocytes, adipocytes, myocytes, and beta cells 24 .…”
Section: Egcg Effect In Metabolic Tissuesmentioning
Green tea and coffee consumption have been widely popular worldwide. These beverages contain caffeine to activate the central nervous system by adenosine receptor blockade, and due to the caffeine, addiction or tolerance may occur. In addition to this caffeine effect, green tea and coffee consumption have always been at the center of discussions about human health, disease, and longevity. In particular, green tea catechins are involved in many biological activities such as antioxidation and modulation of various cellular lipid and proteins. Thus, they are beneficial against degenerative diseases, including obesity, cancer, cardiovascular diseases, and various inflammatory diseases. Some reports also suggest that daily consumption of tea catechins may help in controlling type 2 diabetes. However, other studies have reported that chronic consumption of green tea may result in hepatic failure, neuronal damage, and exacerbation of diabetes, suggesting that interindividual variations in the green tea effect are large. This review will focus on the effect of green tea catechins extracted from the Camellia sinensis plant on type 2 diabetes and obesity, and the possible mechanistic explanation for the experimental results mainly from our laboratory. It is hoped that green tea can be consumed in a suitable manner as a supplement to prevent the development of type 2 diabetes and obesity.
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