Background Retinol binding protein 4 （RBP4）, as an adipocyte secreted cytokine, was recently found to be inversely correlated with expression of glucose transporter 4 （GLUT4） in insulin resistance （IR） state and...Background Retinol binding protein 4 （RBP4）, as an adipocyte secreted cytokine, was recently found to be inversely correlated with expression of glucose transporter 4 （GLUT4） in insulin resistance （IR） state and to have an intimate relationship with IR and type 2 diabetes mellitus （T2DM）. The present study aimed to evaluate the anti-diabetic efficacy of cinnamaldehyde （Cin）, berberine （Ber）, and metformin （Met） as well as their impacts on the RBP4-GLUT4 system. Methods Rat models of T2DM were established by combination of intraperitoneal injection of low-dose streptozotocin and high fat diet induction. Rats were divided into five groups： the control group, the diabetes group, the diabetes＋Ber group, the diabetes＋Cin group, and the diabetes＋Met group. Western blotting was used to detect the serum or tissue RBP4 and GLUT4 protein levels. Results After treatment for four weeks, both Cin and Ber displayed significant hypolipidemic, hypoglycemic, and insulin sensitizing functions （P 〈0.01） compared with the control group. Their effects on lowering fasting plasma glucose （FPG）, low density lipoprotein-cholesterol （LDL-C） and homeostasis model assessment of insulin resistance （HOMA-IR） seem even better than that of Met. Cin and Ber markedly lowered serum RBP4 levels and up-regulated the expression of tissue GLUT4 protein, and Cin seemed more notable in affecting these two proteins. Conclusions Both Cin and Ber display an exciting anti-diabetic efficacy in this study and may be of great value for the treatment of type 2 diabetes. Their mechanisms involve the RBP4-GLUT4 system, during which the serum RBP4 levels are lowered and the expression of tissue GLUT4 protein is up-regulated.展开更多
Objective： To explore the molecular mechanism of puerarin （Pue） in improving insulin resistance through observing its effect on the insulin resistance of 3T3-Li lipocyte induced by free fatty acid （FFA）. Methods...Objective： To explore the molecular mechanism of puerarin （Pue） in improving insulin resistance through observing its effect on the insulin resistance of 3T3-Li lipocyte induced by free fatty acid （FFA）. Methods： 3T3-L1 preadipocyte was induced by a culture solution containing insulin, isobutyo-menthyl-xanthine, and dexamethasone to mature lipocyte, and it was divided into six groups： the control group （normal cells）, the model group （untreated model cells）, and the four drug treatment group exposed to dimethyl biguanide （Met group）, high- dose pueradn （PueH group）, low-dose puerarin （PueL group）, and propylene glycol （PG group）, respectively. Mature lipocytes in various groups, except those in the normal group, were established into insulin resistance model by FFA induction and treated respectively with corresponding drugs. Peroxisome proliferator-activated receptor- γ （PPAR- γ） mRNA expressions at the fourth, sixth, and eighth day were observed using reverse transcription polymerase chain reaction （RT-PCR）; glucose transportation in various groups were observed by 2-deoxy-[3H]-D-glucose intake method; mRNA expression of Cbl binding protein （CAP） was determined by RT-PCR; and glucose transporter-4 （Glut-4） transposition was detected by immune-fluorescence method. Results： PPAR- γmRNA expression increased gradually, and it showed lower levels at the fourth, sixth, and eighth day in all treatment groups than that in the model group. Glucose transportation determination showed that the transportation in the model group was 2.23 ± 0.63, significantly lower than that in the normal group 5.05 ± 0.66 （P〈0.01）; as compared with the model group, they were significantly higher in the PueH and the PueL groups. In addition, the CAP mRNA expression and membranous distribution of Glut-4 were higher in the two Pue treated groups than those in the model group, respectively. Conclusion： Pue could markedly improve the insulin resistance of 3T3-L1 lipocyte, which展开更多
Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)a...Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)and is the primary cause for liver transplantation in the western world.Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of typeⅡdiabetes.Insulin resistance plays an important role in the development of various complications associated with HCV infection.Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis,steatosis,HCC and resistance to anti-viral treatment.Thus,HCV associated insulin resistance is a therapeutic target at any stage of HCV infection.HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway.Various mechanisms have been proposed in regard to HCV mediated insulin resistance,involving up regulation of inflammatory cytokines,like tumor necrosis factor-α,phosphorylation of insulin-receptor substrate-1,Akt,up-regulation of gluconeogenic genes like glucose 6 phosphatase,phosphoenolpyruvate carboxykinase 2,and accumulation of lipid droplets.In this review,we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.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
文摘Background Retinol binding protein 4 （RBP4）, as an adipocyte secreted cytokine, was recently found to be inversely correlated with expression of glucose transporter 4 （GLUT4） in insulin resistance （IR） state and to have an intimate relationship with IR and type 2 diabetes mellitus （T2DM）. The present study aimed to evaluate the anti-diabetic efficacy of cinnamaldehyde （Cin）, berberine （Ber）, and metformin （Met） as well as their impacts on the RBP4-GLUT4 system. Methods Rat models of T2DM were established by combination of intraperitoneal injection of low-dose streptozotocin and high fat diet induction. Rats were divided into five groups： the control group, the diabetes group, the diabetes＋Ber group, the diabetes＋Cin group, and the diabetes＋Met group. Western blotting was used to detect the serum or tissue RBP4 and GLUT4 protein levels. Results After treatment for four weeks, both Cin and Ber displayed significant hypolipidemic, hypoglycemic, and insulin sensitizing functions （P 〈0.01） compared with the control group. Their effects on lowering fasting plasma glucose （FPG）, low density lipoprotein-cholesterol （LDL-C） and homeostasis model assessment of insulin resistance （HOMA-IR） seem even better than that of Met. Cin and Ber markedly lowered serum RBP4 levels and up-regulated the expression of tissue GLUT4 protein, and Cin seemed more notable in affecting these two proteins. Conclusions Both Cin and Ber display an exciting anti-diabetic efficacy in this study and may be of great value for the treatment of type 2 diabetes. Their mechanisms involve the RBP4-GLUT4 system, during which the serum RBP4 levels are lowered and the expression of tissue GLUT4 protein is up-regulated.
文摘Objective： To explore the molecular mechanism of puerarin （Pue） in improving insulin resistance through observing its effect on the insulin resistance of 3T3-Li lipocyte induced by free fatty acid （FFA）. Methods： 3T3-L1 preadipocyte was induced by a culture solution containing insulin, isobutyo-menthyl-xanthine, and dexamethasone to mature lipocyte, and it was divided into six groups： the control group （normal cells）, the model group （untreated model cells）, and the four drug treatment group exposed to dimethyl biguanide （Met group）, high- dose pueradn （PueH group）, low-dose puerarin （PueL group）, and propylene glycol （PG group）, respectively. Mature lipocytes in various groups, except those in the normal group, were established into insulin resistance model by FFA induction and treated respectively with corresponding drugs. Peroxisome proliferator-activated receptor- γ （PPAR- γ） mRNA expressions at the fourth, sixth, and eighth day were observed using reverse transcription polymerase chain reaction （RT-PCR）; glucose transportation in various groups were observed by 2-deoxy-[3H]-D-glucose intake method; mRNA expression of Cbl binding protein （CAP） was determined by RT-PCR; and glucose transporter-4 （Glut-4） transposition was detected by immune-fluorescence method. Results： PPAR- γmRNA expression increased gradually, and it showed lower levels at the fourth, sixth, and eighth day in all treatment groups than that in the model group. Glucose transportation determination showed that the transportation in the model group was 2.23 ± 0.63, significantly lower than that in the normal group 5.05 ± 0.66 （P〈0.01）; as compared with the model group, they were significantly higher in the PueH and the PueL groups. In addition, the CAP mRNA expression and membranous distribution of Glut-4 were higher in the two Pue treated groups than those in the model group, respectively. Conclusion： Pue could markedly improve the insulin resistance of 3T3-L1 lipocyte, which
基金Supported by The National Institutes of Health,NO.DK080812
文摘Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)and is the primary cause for liver transplantation in the western world.Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of typeⅡdiabetes.Insulin resistance plays an important role in the development of various complications associated with HCV infection.Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis,steatosis,HCC and resistance to anti-viral treatment.Thus,HCV associated insulin resistance is a therapeutic target at any stage of HCV infection.HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway.Various mechanisms have been proposed in regard to HCV mediated insulin resistance,involving up regulation of inflammatory cytokines,like tumor necrosis factor-α,phosphorylation of insulin-receptor substrate-1,Akt,up-regulation of gluconeogenic genes like glucose 6 phosphatase,phosphoenolpyruvate carboxykinase 2,and accumulation of lipid droplets.In this review,we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.
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.
