Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes m...Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control group(P<0.05),but there was no significant difference between the insulin group and metformin group(P>0.05).Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher,while triglyceride was significantly lower than the one in the control group(P<0.05);triglyceride level of rats in the insulin group was significantly higher than the one in the metformin group(P<0.05).There was no significant difference in insulin and leptin level of offspring rats between the insulin group and metformin group(P>0.05).Conclusions:GDM can induce the methylation of PPARGC1 A of offspring rats to reduce the expression of PPARGC1 A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up;the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1 A and thus improve the abnormal glycolipid metabolism of offspring rats.展开更多
When cultured in medium limited of nitrogen sources, the phytopathogen Ustilago maydis produces two amphipathic glycolipids: Ustilagic acid (UA) and Mannosylerythritol lipid (MEL), which in addition to the hydrophilic...When cultured in medium limited of nitrogen sources, the phytopathogen Ustilago maydis produces two amphipathic glycolipids: Ustilagic acid (UA) and Mannosylerythritol lipid (MEL), which in addition to the hydrophilic moiety, contain dior tri-hydroxylated C16 fatty acids (UA), or C8 and C16 saturated fatty acids (MEL). We compared the growth and morphology of cells in YPD and in minimum media containing glucose and nitrogen sources such as nitrate or urea and those deprived of nitrogen. Nitrogen-starved cells showed a dramatic accumulation of internal lipids identified as lipid droplets when stained with the hydrophobic probe BODIPY;these lipid droplets were enriched in unsaturated fatty acids. Fatty acids in YPD or medium containing nitrate as nitrogen source showed a combination of saturated/unsaturated lipids, but when urea was the nitrogen source, cells only contained saturated fatty acids. The glycolipid profiles produced in the presence or absence of nitrogen showed preferences towards the production of one kind of glycolipid: cells in media containing nitrate or urea produced different proportions of UA/MEL, but under nitrogen starvation cells contained only UA. The emulsification capacity of the glycolipids produced in media with or without nitrogen was similar (72% - 76%). HPLC of the glycolipids allowed the separation of fractions with different emulsifying characteristics. Our results indicate that U. maydis accumulates lipid droplets when deprived of nitrogen source and confirm that UA is not under nitrogen control, but rather that MEL and lipid droplets are produced and oppositely regulated by nitrogen.展开更多
To evaluate the sperm motility stimulating activity of a sulfono glycolipid (S-ACT-l) isolated from Gelidiella acerosa, a Sri Lankan marine red algae. Methods: S-ACT-l, a white amorphous powder was separated from more...To evaluate the sperm motility stimulating activity of a sulfono glycolipid (S-ACT-l) isolated from Gelidiella acerosa, a Sri Lankan marine red algae. Methods: S-ACT-l, a white amorphous powder was separated from more polar fractions of the hexane soluble of 1:1 CH2Cl2/MeOH extract and subjected to 1H, 1 3C NMR and IR Spectroscopy after reverse phase HPLC for identification. Effects of S-ACT-1 on human sperm motility was assessed in vitro at 10,100 and 1000μg/Ml concentrations at 37℃ for 0, 5, 15, 30 and 60 min. Results: S-ACT-1 was identified as a glycolipid sulfate. The lower dose increased the sperm motility slightly, whilst the medium dose significantly increased the motility ( P ＜ 0.05) from 5 min of incubation reaching a peak at 15 min and the stimulant effect was sustained throughout the experimental period. Furthermore, the medium dose rendered 80% of the immotile viable sperm motile.In contrast, the highest dose impaired the sperm motility. The sperm stimulating activity of S-ACT-1 was dose-depen dent and had a bell-shaped dose response curve for all the 5 incubation periods. Conclusion: S-ACT-1 of Gelidiella acerosa is a Sulfono glycolipid. S-ACT-1 has a potent sperm motility stimulating activity in vitro and has the potential to be developed into a sperm stimulant.展开更多
Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2...Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.展开更多
目的探究参芪降糖颗粒辅治对2型糖尿病(Diabetes mellitus type 2,T2DM)患者糖脂代谢平衡的作用效果,并分析对其转化生长因子-β1(Transforming growth factor-β1,TGF-β1)、胰高糖素样肽-1(Glucagon-like peptide-1,GLP-1)的影响。方...目的探究参芪降糖颗粒辅治对2型糖尿病(Diabetes mellitus type 2,T2DM)患者糖脂代谢平衡的作用效果,并分析对其转化生长因子-β1(Transforming growth factor-β1,TGF-β1)、胰高糖素样肽-1(Glucagon-like peptide-1,GLP-1)的影响。方法选取2018年12月—2021年12月期间在四川省眉山市中医医院初诊为T2DM患者96例为研究对象,按随机数字表法分为对照组和观察组,每组各48例。对照组采取常规西药治疗,观察组在对照组基础上采用参芪降糖颗粒加以辅治。治疗4周后,观察比较两组患者临床疗效、治疗前后糖脂[空腹血糖(Fasting plasma glucose,FPG)、餐后2 h血糖(2 h postprandial glucose,2 h PG)、糖化血红蛋白(Glycosylated hemoglobin,HbA1c)以及甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low-density lipoprotein cholesterol,LDL-C)]代谢情况、TGF-β1及GLP-1水平变化,同时探究药物安全性。结果治疗后观察组显效43.75%(21/48)、总有效率95.83%(46/48)均明显高于对照组22.92%(11/48)、83.33%(40/48),差异有统计学意义(P<0.05)。治疗4周后两组患者糖代谢指标FPG、2 h PG、HbA1c和脂代谢指标TG、TC、LDL-C均较治疗前明显降低,HDL-C较治疗前明显升高,差异有统计学意义(P<0.05);且观察组糖代谢指标FPG、2 h PG、HbA1c和脂代谢指标TG、TC、LDL-C均低于对照组,HDL-C高于对照组,差异有统计学意义(P<0.05)。治疗4周后两组患者TGF-β1水平较治疗前降低,GLP-1水平较治疗前升高,差异有统计学意义(P<0.05);且观察组TGF-β1水平低于对照组,GLP-1水平高于对照组,差异有统计学意义(P<0.05)。时点效应可显著影两项指标水平,且两项指标随时点变化趋势受到治疗方法的干预(P<0.05)。结论在西药基础上辅以参芪降糖颗粒可以明显降低T2DM患者的血糖和血脂水平,有效改善机体糖脂代谢和胰岛素代谢,从而提高整体疗效。展开更多
Objective: To investigate the protective effects of modified Linggui Zhugan Decoction(MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus(T2 DM) rats. Methods:Fifty Sprague-Dawley rats wer...Objective: To investigate the protective effects of modified Linggui Zhugan Decoction(MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus(T2 DM) rats. Methods:Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2 DM(ob-T2 DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M,9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups,10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance(IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase(PI3 K)-protein kinase B(PKB or Akt)/the mammalian target of rapamycin(mTOR)-ribosome protein subunit 6 kinase 1(S6 K1)/AMP-activated protein kinase(AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α) pathways were also studied. Results: MLZD dose-dependently reduced fasting blood glucose,fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2 DM rats(P<0.05). Similarly, total cholesterol, triglyceride, low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2 DM rats after 4-week treatment(P<0.05 or P<0.01).Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6(P<0.05 or P<0.01). MLZD regulated the PI3 K-Akt/mTOR-S6 K1/AMPK-PGC-1α pathways and restored the tissue structure of liver and pancreas(P<0.05 or P<0.01). Conclusions: MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3 K-Akt/mTOR-S6 K1/AMPK-PGC-1α pathways.展开更多
Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed th...Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.展开更多
Objective:To explore the mechanisms of Dangua Recipe(DGR)in improving glycolipid metabolism based on transcriptomics.Methods:Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a rand...Objective:To explore the mechanisms of Dangua Recipe(DGR)in improving glycolipid metabolism based on transcriptomics.Methods:Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table,including a conventional diet group(Group A),a DGR group(Group B,high-calorie diet+20.5 g DGR),and a high-calorie fodder model group(Group C).After 12 weeks of intervention,the liver tissue of rats was taken.Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy,and then gene or protein validation of liver tissue were performed.Nicotinamide phosphoribosyl transferase(Nampt)and phosphoenolpyruvate carboxykinase(PEPCK)proteins in liver tissues were detected by enzyme linked immunosorbent assay,fatty acid synthase(FASN)protein was detected by Western blot,and fatty acid binding protein 5(FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction.Furthermore,the functional verification was performed on the diabetic model rats by Nampt blocker(GEN-617)injected in vivo.Hemoglobin A1c(HbA1c),plasma total cholesterol and triglycerides were detected.Results:Totally,257 differentialdominant genes of Group A vs.Group C and 392 differential-dominant genes of Group B vs.Group C were found.Moreover,11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs.Group C and Group C vs.Group B were confirmed.The liver tissue target validation showed that Nampt,FASN,PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome.The in vivo functional tests showed that GEN-617 increased body weight,HbA1c,triglyceride and total cholesterol levels in the diabetic rats(P<0.05 or P<0.01);while all the above-mentioned levels(except triglyceride)were decreased significantly by GEN-617 combined with DGR intervention(P<0.05 or P<0.01).Conclusion:Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.展开更多
Glycosylated lipids(GLs)are added-value lipid derivatives of great potential.Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents,they have diverse biologica...Glycosylated lipids(GLs)are added-value lipid derivatives of great potential.Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents,they have diverse biological activities with promising biomedical and cosmeceutical applications.Glycolipids,especially those of microbial origin,have interesting antimicrobial,anticancer,antiparasitic as well as immunomodulatory activities.Nonetheless,GLs are hardly accessing the market because of their high cost of production.We believe that experience of metabolic engineering(ME)of microbial lipids for biofuel production can now be harnessed towards a successful synthesis of microbial GLs for biomedical and other applications.This review presents chemical groups of bacterial and fungal GLs,their biological activities,their general biosynthetic pathways and an insight on ME strategies for their production.展开更多
基金supported by Shandong Natural Science Fund(Y2008c170)
文摘Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control group(P<0.05),but there was no significant difference between the insulin group and metformin group(P>0.05).Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher,while triglyceride was significantly lower than the one in the control group(P<0.05);triglyceride level of rats in the insulin group was significantly higher than the one in the metformin group(P<0.05).There was no significant difference in insulin and leptin level of offspring rats between the insulin group and metformin group(P>0.05).Conclusions:GDM can induce the methylation of PPARGC1 A of offspring rats to reduce the expression of PPARGC1 A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up;the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1 A and thus improve the abnormal glycolipid metabolism of offspring rats.
文摘When cultured in medium limited of nitrogen sources, the phytopathogen Ustilago maydis produces two amphipathic glycolipids: Ustilagic acid (UA) and Mannosylerythritol lipid (MEL), which in addition to the hydrophilic moiety, contain dior tri-hydroxylated C16 fatty acids (UA), or C8 and C16 saturated fatty acids (MEL). We compared the growth and morphology of cells in YPD and in minimum media containing glucose and nitrogen sources such as nitrate or urea and those deprived of nitrogen. Nitrogen-starved cells showed a dramatic accumulation of internal lipids identified as lipid droplets when stained with the hydrophobic probe BODIPY;these lipid droplets were enriched in unsaturated fatty acids. Fatty acids in YPD or medium containing nitrate as nitrogen source showed a combination of saturated/unsaturated lipids, but when urea was the nitrogen source, cells only contained saturated fatty acids. The glycolipid profiles produced in the presence or absence of nitrogen showed preferences towards the production of one kind of glycolipid: cells in media containing nitrate or urea produced different proportions of UA/MEL, but under nitrogen starvation cells contained only UA. The emulsification capacity of the glycolipids produced in media with or without nitrogen was similar (72% - 76%). HPLC of the glycolipids allowed the separation of fractions with different emulsifying characteristics. Our results indicate that U. maydis accumulates lipid droplets when deprived of nitrogen source and confirm that UA is not under nitrogen control, but rather that MEL and lipid droplets are produced and oppositely regulated by nitrogen.
文摘To evaluate the sperm motility stimulating activity of a sulfono glycolipid (S-ACT-l) isolated from Gelidiella acerosa, a Sri Lankan marine red algae. Methods: S-ACT-l, a white amorphous powder was separated from more polar fractions of the hexane soluble of 1:1 CH2Cl2/MeOH extract and subjected to 1H, 1 3C NMR and IR Spectroscopy after reverse phase HPLC for identification. Effects of S-ACT-1 on human sperm motility was assessed in vitro at 10,100 and 1000μg/Ml concentrations at 37℃ for 0, 5, 15, 30 and 60 min. Results: S-ACT-1 was identified as a glycolipid sulfate. The lower dose increased the sperm motility slightly, whilst the medium dose significantly increased the motility ( P ＜ 0.05) from 5 min of incubation reaching a peak at 15 min and the stimulant effect was sustained throughout the experimental period. Furthermore, the medium dose rendered 80% of the immotile viable sperm motile.In contrast, the highest dose impaired the sperm motility. The sperm stimulating activity of S-ACT-1 was dose-depen dent and had a bell-shaped dose response curve for all the 5 incubation periods. Conclusion: S-ACT-1 of Gelidiella acerosa is a Sulfono glycolipid. S-ACT-1 has a potent sperm motility stimulating activity in vitro and has the potential to be developed into a sperm stimulant.
基金funded by the National Key Research and Development Program of China(2020YFD0900902)Zhejiang Province Public Welfare Technology Application Research Project(LGJ21C20001)Zhejiang Provincial Key Research and Development Project of China(2019C02076 and 2019C02075)。
文摘Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.
文摘目的探究参芪降糖颗粒辅治对2型糖尿病(Diabetes mellitus type 2,T2DM)患者糖脂代谢平衡的作用效果,并分析对其转化生长因子-β1(Transforming growth factor-β1,TGF-β1)、胰高糖素样肽-1(Glucagon-like peptide-1,GLP-1)的影响。方法选取2018年12月—2021年12月期间在四川省眉山市中医医院初诊为T2DM患者96例为研究对象,按随机数字表法分为对照组和观察组,每组各48例。对照组采取常规西药治疗,观察组在对照组基础上采用参芪降糖颗粒加以辅治。治疗4周后,观察比较两组患者临床疗效、治疗前后糖脂[空腹血糖(Fasting plasma glucose,FPG)、餐后2 h血糖(2 h postprandial glucose,2 h PG)、糖化血红蛋白(Glycosylated hemoglobin,HbA1c)以及甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low-density lipoprotein cholesterol,LDL-C)]代谢情况、TGF-β1及GLP-1水平变化,同时探究药物安全性。结果治疗后观察组显效43.75%(21/48)、总有效率95.83%(46/48)均明显高于对照组22.92%(11/48)、83.33%(40/48),差异有统计学意义(P<0.05)。治疗4周后两组患者糖代谢指标FPG、2 h PG、HbA1c和脂代谢指标TG、TC、LDL-C均较治疗前明显降低,HDL-C较治疗前明显升高,差异有统计学意义(P<0.05);且观察组糖代谢指标FPG、2 h PG、HbA1c和脂代谢指标TG、TC、LDL-C均低于对照组,HDL-C高于对照组,差异有统计学意义(P<0.05)。治疗4周后两组患者TGF-β1水平较治疗前降低,GLP-1水平较治疗前升高,差异有统计学意义(P<0.05);且观察组TGF-β1水平低于对照组,GLP-1水平高于对照组,差异有统计学意义(P<0.05)。时点效应可显著影两项指标水平,且两项指标随时点变化趋势受到治疗方法的干预(P<0.05)。结论在西药基础上辅以参芪降糖颗粒可以明显降低T2DM患者的血糖和血脂水平,有效改善机体糖脂代谢和胰岛素代谢,从而提高整体疗效。
基金Supported by the National Natural Science Foundation of China (No. 81302877)Science and Technology Project of Guangdong Province of China (No. 2014A020212056)。
文摘Objective: To investigate the protective effects of modified Linggui Zhugan Decoction(MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus(T2 DM) rats. Methods:Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2 DM(ob-T2 DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M,9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups,10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance(IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase(PI3 K)-protein kinase B(PKB or Akt)/the mammalian target of rapamycin(mTOR)-ribosome protein subunit 6 kinase 1(S6 K1)/AMP-activated protein kinase(AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α) pathways were also studied. Results: MLZD dose-dependently reduced fasting blood glucose,fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2 DM rats(P<0.05). Similarly, total cholesterol, triglyceride, low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2 DM rats after 4-week treatment(P<0.05 or P<0.01).Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6(P<0.05 or P<0.01). MLZD regulated the PI3 K-Akt/mTOR-S6 K1/AMPK-PGC-1α pathways and restored the tissue structure of liver and pancreas(P<0.05 or P<0.01). Conclusions: MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3 K-Akt/mTOR-S6 K1/AMPK-PGC-1α pathways.
基金supported by the National Natural Science Foundation of China(81321004,81621064,Jiandong Jiang81322050,Zonggen Peng)+2 种基金National Mega-Project for “R&D for Innovative drugs”,Ministry of Science and Technology,China(2012ZX09301-002-001,Jiandong Jiang,2018ZX09711001-003-010,Zonggen Peng)Ministry of Education,China(NCET-12-0072,Zonggen Peng)CAMS Innovation Fund for Medical Sciences,China(CIFMS)(2017-I2M-3-012,Zonggen Peng)
文摘Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.
基金the National Natural Science Foundation of China(No.81873213,81473550)the Natural Science Foundation of Fujian Province(No.2017J01213,2016J0146)the Inn ovation Fund of Medical Science of Fujian Provi nee(No.2017-CX-42),China。
文摘Objective:To explore the mechanisms of Dangua Recipe(DGR)in improving glycolipid metabolism based on transcriptomics.Methods:Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table,including a conventional diet group(Group A),a DGR group(Group B,high-calorie diet+20.5 g DGR),and a high-calorie fodder model group(Group C).After 12 weeks of intervention,the liver tissue of rats was taken.Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy,and then gene or protein validation of liver tissue were performed.Nicotinamide phosphoribosyl transferase(Nampt)and phosphoenolpyruvate carboxykinase(PEPCK)proteins in liver tissues were detected by enzyme linked immunosorbent assay,fatty acid synthase(FASN)protein was detected by Western blot,and fatty acid binding protein 5(FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction.Furthermore,the functional verification was performed on the diabetic model rats by Nampt blocker(GEN-617)injected in vivo.Hemoglobin A1c(HbA1c),plasma total cholesterol and triglycerides were detected.Results:Totally,257 differentialdominant genes of Group A vs.Group C and 392 differential-dominant genes of Group B vs.Group C were found.Moreover,11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs.Group C and Group C vs.Group B were confirmed.The liver tissue target validation showed that Nampt,FASN,PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome.The in vivo functional tests showed that GEN-617 increased body weight,HbA1c,triglyceride and total cholesterol levels in the diabetic rats(P<0.05 or P<0.01);while all the above-mentioned levels(except triglyceride)were decreased significantly by GEN-617 combined with DGR intervention(P<0.05 or P<0.01).Conclusion:Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.
基金This work was funded by the United States Department of Energy-Chicago(DoE-Chicago)grant DE-SC0008744 to Professor Gregory StephanopoulosDr.Ahmad M.Abdel-Mawgoud is funded by a postdoctoral fellowship from the Natural Sciences and Engineering Research Council of Canada(NSERC),funding reference number PDF-488195-2016,and partly by the US DoE grant DESC0008744 mentioned above。
文摘Glycosylated lipids(GLs)are added-value lipid derivatives of great potential.Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents,they have diverse biological activities with promising biomedical and cosmeceutical applications.Glycolipids,especially those of microbial origin,have interesting antimicrobial,anticancer,antiparasitic as well as immunomodulatory activities.Nonetheless,GLs are hardly accessing the market because of their high cost of production.We believe that experience of metabolic engineering(ME)of microbial lipids for biofuel production can now be harnessed towards a successful synthesis of microbial GLs for biomedical and other applications.This review presents chemical groups of bacterial and fungal GLs,their biological activities,their general biosynthetic pathways and an insight on ME strategies for their production.
