Nuciferine contained in lotus leaves have been confirmed to have the effect of ameliorating hyperlipemia and hyperglycemia.A laser scanning confocal microscope was used to track the translocation of glucose transporte...Nuciferine contained in lotus leaves have been confirmed to have the effect of ameliorating hyperlipemia and hyperglycemia.A laser scanning confocal microscope was used to track the translocation of glucose transporter 4(GLUT4)in L6 cells and the changes in intracellular Ca^(2+)levels in real time,and related protease inhibitors combined with western blotting were used to explore the mechanism of nuciferine.Meanwhile,KK-Ay mice,the spontaneous type 2 diabetic mice,were used to evaluate the in vivo activity of nuciferine.In this study,the in vitro studies indicated that nuciferine-induced GLUT4 translocation was regulated by G protein-PLC-PKC and AMPK pathways and nuciferine-enhanced intracellular Ca^(2+)was mediated by G protein-PLC-IP3-IP3R pathway,the increase in intracellular Ca^(2+)caused by nuciferine was not directly related to GLUT4 translocation,but both promote glucose uptake.The in vivo results suggested that nuciferine ameliorated weight gain induced by high-fat diet,abnormal lipid metabolism and the symptoms of insulin resistance in KK-Ay diabetic mice.Western blot results suggested that nuciferine increased AMPK and PKC phosphorylation levels in skeletal muscle and liver,and enhanced GLUT4 expression in skeletal muscle.Taken together,this research showed that nuciferine has the non-negligible potential in the treatment of type 2 diabetes mellitus.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
Objective To evaluate the effect of low-dose insulin [1 U/(kg·d)] in combination with selenium [180 g/(kg·d)] on general physiological parameters and glucose transporter (GLUT4) level in skeletal muscle of s...Objective To evaluate the effect of low-dose insulin [1 U/(kg·d)] in combination with selenium [180 g/(kg·d)] on general physiological parameters and glucose transporter (GLUT4) level in skeletal muscle of streptozotocin (STZ)-induced diabetic rats. Methods Diabetic rats were treated with insulin,selenium,and insulin and selenium in combination for four weeks. The level of blood glucose was determined using One Touch SureStep Blood Glucose meter and the level of GLUT4 in skeletal muscle was examined by immunoblotting and immunohistochemistry. Results Our data showed that insulin in combination with selenium could significantly lower blood glucose level and restore the disturbance in GLUT4 level in skeletal muscle. Treatment with insulin was only partially effective in restoring diabetic alterations. Conclusion It can be concluded that there is a synergistic action between insulin and selenium,and that treatment of diabetic rats with combined doses of insulin and selenium is effective in the normalization of blood glucose level and correction of altered GLUT4 distribution in skeletal muscle of diabetic rats.展开更多
Glucose is vital to embryogenesis,as are glucose transporters.Glucose transporter 4(Glut4)is one of the glucose transporters,which is involved in rapid uptake of glucose by various cells and promotes glucose homeostas...Glucose is vital to embryogenesis,as are glucose transporters.Glucose transporter 4(Glut4)is one of the glucose transporters,which is involved in rapid uptake of glucose by various cells and promotes glucose homeostasis.Although energy metabolism in insect reproduction is well known,the molecular mechanism of Glut4 in insect reproduction is poorly understood.We suspect that Glut4 is involved in maintaining glucose concentrations in the ovaries and affecting vitellogenesis,which is critical for subsequent oocyte maturation and insect fertility.Harmonia axyridis(Pallas)is a model organism for genetic research and a natural enemy of insect pests.We studied the influence of the Glut4 gene on the reproduction and development of H.axyridis using RNA interference technology.Reverse transcription quantitative polymerase chain reaction analysis revealed that HaGlut4 was most highly expressed in adults.Knockdown of the HaGlut4 gene reduced the transcript levels of HaGlut4,and the weight and number of eggs produced significantly decreased.In addition,the transcript levels of vitellogenin receptor and vitellogenin in the fat bodies and the ovaries of H.axyridis decreased after the interference of Glut4,and decreased the triglyceride,fatty acid,total amino acid and adenosine triphosphate content of H.axyridis.This resulted in severe blockage of ovary development and reduction of yolk formation;there was no development of ovarioles in the developing oocytes.These changes indicate that a lack of HaGlut4 can impair ovarian development and oocyte maturation and result in decreased fecundity.展开更多
Melatonin receptor 1B(MT2,encoded by the MTNR1B gene),a high-affinity receptor for melatonin,is associated with glucose homeostasis including glucose uptake and transport.The rs10830963 variant in the MTNR1B gene is l...Melatonin receptor 1B(MT2,encoded by the MTNR1B gene),a high-affinity receptor for melatonin,is associated with glucose homeostasis including glucose uptake and transport.The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus(GDM);however,the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood.This article aims to investigate the relationship between rs10830963 variants and GDM development,as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts.TaqMan-MGB(minor groove binder)probe quantitative realtime polymerase chain reaction(qPCR)assays were used for rs10930963 genotyping.MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence,western blot,and qPCR.The relationship between MT2 and glucose transporters(GLUTs)or peroxisome proliferator-activated receptorγ(PPARγ)was established by western blot,and glucose consumption of trophoblasts was measured by a glucose assay kit.The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women(P<0.05).The fasting,1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers(P<0.05).Besides,the protein and messenger RNA(mRNA)expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women(P<0.05).Melatonin could stimulate glucose uptake and GLUT4 and PPARγprotein expression in trophoblasts,which could be attenuated by MT2 receptor knockdown.In conclusion,the rs10830963 variant was associated with an increased risk of GDM.The MT2 receptor is essential for melatonin to raise glucose uptake and transport,which may be mediated by PPARγ.展开更多
A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles (GCNPs), was developed for specific recognition and interaction with glucose transporters (Gluts) over-expressed by tumor cells. GC ...A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles (GCNPs), was developed for specific recognition and interaction with glucose transporters (Gluts) over-expressed by tumor cells. GC was synthesized by using succinic acid as a linker between glucosamine and chitosan (CS), and successful synthesis was confirmed by NMR and elemental analysis. GCNPs were prepared by ionic crosslinking method, and characterized in terms of morphology, size, and zeta potential. The optimally prepared nanoparticles showed spherical shapes with an average particle size of (187.9 ± 3.8) nm and a zeta potential of (-15.43 ± 0.31) mV. The GCNPs showed negligible cytotoxicity to mouse embryo fibroblast and 4T1 cells. Doxorubicin (DOX) could be efficiently entrapped into GCNPs, with a loading capacity and encapsulation efficiency of 20.11% and 64.81%, respectively. DOX-Ioaded nanoparticles exhibited sustained-release behavior in phosphate buffered saline (pH 7.4). In vitro cellular uptake studies showed that the GCNPs had better endocytosis ability than CSNPs, and the antitumor activity of DOX/GCNPs was 4-5 times effectiveness in 4T1 cell killing than that of DOX/CSNPs. All the results demonstrate that nanoparticles decorated with glucose have specific interactions with cancer cells via the recognition between glucose and Gluts. Therefore, Gluts-targeted GCNPs may be promising delivery agents in cancer therapies.展开更多
基金financially supported by National Natural Science Foundation of China grants(81573561,81911540487,31070744)the Fundamental Research Funds for the Central Universities,South-Central University for Nationalities(CZR18003).
文摘Nuciferine contained in lotus leaves have been confirmed to have the effect of ameliorating hyperlipemia and hyperglycemia.A laser scanning confocal microscope was used to track the translocation of glucose transporter 4(GLUT4)in L6 cells and the changes in intracellular Ca^(2+)levels in real time,and related protease inhibitors combined with western blotting were used to explore the mechanism of nuciferine.Meanwhile,KK-Ay mice,the spontaneous type 2 diabetic mice,were used to evaluate the in vivo activity of nuciferine.In this study,the in vitro studies indicated that nuciferine-induced GLUT4 translocation was regulated by G protein-PLC-PKC and AMPK pathways and nuciferine-enhanced intracellular Ca^(2+)was mediated by G protein-PLC-IP3-IP3R pathway,the increase in intracellular Ca^(2+)caused by nuciferine was not directly related to GLUT4 translocation,but both promote glucose uptake.The in vivo results suggested that nuciferine ameliorated weight gain induced by high-fat diet,abnormal lipid metabolism and the symptoms of insulin resistance in KK-Ay diabetic mice.Western blot results suggested that nuciferine increased AMPK and PKC phosphorylation levels in skeletal muscle and liver,and enhanced GLUT4 expression in skeletal muscle.Taken together,this research showed that nuciferine has the non-negligible potential in the treatment of type 2 diabetes mellitus.
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.
基金supported by the National Basic Research Program of China (973Program) ( No.2007CB512005)the National Natural Science Foundation of China (No.30770785)+1 种基金the Cultivation Fund of the Key Scientific and Technological Innovation Pro-ject of the Ministry of Education of China (No.705045)the Specialized Research Fund for the Doctoral Program of Higher Education(No.20050698012)
文摘Objective To evaluate the effect of low-dose insulin [1 U/(kg·d)] in combination with selenium [180 g/(kg·d)] on general physiological parameters and glucose transporter (GLUT4) level in skeletal muscle of streptozotocin (STZ)-induced diabetic rats. Methods Diabetic rats were treated with insulin,selenium,and insulin and selenium in combination for four weeks. The level of blood glucose was determined using One Touch SureStep Blood Glucose meter and the level of GLUT4 in skeletal muscle was examined by immunoblotting and immunohistochemistry. Results Our data showed that insulin in combination with selenium could significantly lower blood glucose level and restore the disturbance in GLUT4 level in skeletal muscle. Treatment with insulin was only partially effective in restoring diabetic alterations. Conclusion It can be concluded that there is a synergistic action between insulin and selenium,and that treatment of diabetic rats with combined doses of insulin and selenium is effective in the normalization of blood glucose level and correction of altered GLUT4 distribution in skeletal muscle of diabetic rats.
基金This work was supported by the National Key Research and Development Program of China(Grant No.2017YFD0201000)the Hangzhou Science and Technology Development Program of China(Grant No.20190101A01).
文摘Glucose is vital to embryogenesis,as are glucose transporters.Glucose transporter 4(Glut4)is one of the glucose transporters,which is involved in rapid uptake of glucose by various cells and promotes glucose homeostasis.Although energy metabolism in insect reproduction is well known,the molecular mechanism of Glut4 in insect reproduction is poorly understood.We suspect that Glut4 is involved in maintaining glucose concentrations in the ovaries and affecting vitellogenesis,which is critical for subsequent oocyte maturation and insect fertility.Harmonia axyridis(Pallas)is a model organism for genetic research and a natural enemy of insect pests.We studied the influence of the Glut4 gene on the reproduction and development of H.axyridis using RNA interference technology.Reverse transcription quantitative polymerase chain reaction analysis revealed that HaGlut4 was most highly expressed in adults.Knockdown of the HaGlut4 gene reduced the transcript levels of HaGlut4,and the weight and number of eggs produced significantly decreased.In addition,the transcript levels of vitellogenin receptor and vitellogenin in the fat bodies and the ovaries of H.axyridis decreased after the interference of Glut4,and decreased the triglyceride,fatty acid,total amino acid and adenosine triphosphate content of H.axyridis.This resulted in severe blockage of ovary development and reduction of yolk formation;there was no development of ovarioles in the developing oocytes.These changes indicate that a lack of HaGlut4 can impair ovarian development and oocyte maturation and result in decreased fecundity.
基金This work was supported by the Health Commission of Hubei Province Scientific Research Project(No.WJ2021M129)the National Key Research and Development Program of China(No.2021YFC2701502)。
文摘Melatonin receptor 1B(MT2,encoded by the MTNR1B gene),a high-affinity receptor for melatonin,is associated with glucose homeostasis including glucose uptake and transport.The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus(GDM);however,the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood.This article aims to investigate the relationship between rs10830963 variants and GDM development,as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts.TaqMan-MGB(minor groove binder)probe quantitative realtime polymerase chain reaction(qPCR)assays were used for rs10930963 genotyping.MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence,western blot,and qPCR.The relationship between MT2 and glucose transporters(GLUTs)or peroxisome proliferator-activated receptorγ(PPARγ)was established by western blot,and glucose consumption of trophoblasts was measured by a glucose assay kit.The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women(P<0.05).The fasting,1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers(P<0.05).Besides,the protein and messenger RNA(mRNA)expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women(P<0.05).Melatonin could stimulate glucose uptake and GLUT4 and PPARγprotein expression in trophoblasts,which could be attenuated by MT2 receptor knockdown.In conclusion,the rs10830963 variant was associated with an increased risk of GDM.The MT2 receptor is essential for melatonin to raise glucose uptake and transport,which may be mediated by PPARγ.
基金This research was supported by the National Natural Science Foundation of China (Grant Nos. 31000423 and 31301420) and the China Postdoctoral Science Foundation (Grant No. 2014M551965).
文摘A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles (GCNPs), was developed for specific recognition and interaction with glucose transporters (Gluts) over-expressed by tumor cells. GC was synthesized by using succinic acid as a linker between glucosamine and chitosan (CS), and successful synthesis was confirmed by NMR and elemental analysis. GCNPs were prepared by ionic crosslinking method, and characterized in terms of morphology, size, and zeta potential. The optimally prepared nanoparticles showed spherical shapes with an average particle size of (187.9 ± 3.8) nm and a zeta potential of (-15.43 ± 0.31) mV. The GCNPs showed negligible cytotoxicity to mouse embryo fibroblast and 4T1 cells. Doxorubicin (DOX) could be efficiently entrapped into GCNPs, with a loading capacity and encapsulation efficiency of 20.11% and 64.81%, respectively. DOX-Ioaded nanoparticles exhibited sustained-release behavior in phosphate buffered saline (pH 7.4). In vitro cellular uptake studies showed that the GCNPs had better endocytosis ability than CSNPs, and the antitumor activity of DOX/GCNPs was 4-5 times effectiveness in 4T1 cell killing than that of DOX/CSNPs. All the results demonstrate that nanoparticles decorated with glucose have specific interactions with cancer cells via the recognition between glucose and Gluts. Therefore, Gluts-targeted GCNPs may be promising delivery agents in cancer therapies.