检索结果-南通市图书馆

Acta Pharmaceutica Sinica B 2014年第2期4卷 135-140页

作者： Jinglong Liu Yi Huan Caina Li Minzhi Liu zhufang shen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Diabetes Research CenterInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Dipeptidyl peptidase 4(DPP4)is recognised as an attractive anti-diabetic drug target,and several DPP4 inhibitors are already on the *** members of the same gene family,dipeptidyl peptidase 8(DPP8)and dipeptidyl peptidase 9(DPP9)share high sequence and structural homology as well as functional activity with ***,the inhibition of their activities was reported to cause severe ***,the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic *** achieve this goal,we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta *** this method,we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression *** optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL,respectively,and the corresponding concentrations of their substrates were both 0.2 mmol/*** method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates,which would provide valuable guidance in the development of safe DPP4 inhibitors.

关键词： DPP4 DPP8 DPP9 Inhibitor Selective evaluation method

A cell-based fluorescent glucose transporter assay for SGLT2 inhibitor discovery

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2013年第2期3卷 97-101页

作者： Yi Huan Linyi Li Quan Liu Shuainan Liu zhufang shen State Key Laboratory of Bioactive Substances and Functions of NaturalMedicines Diabetes Research CenterInstituteof Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China

The sodium/glucose cotransporter 2(SGLT2)is responsible for the majority of glucose reabsorption in the kidney,and currently,SGLT2 inhibitors are considered as promising hypoglycemic agents for the treatment of type 2 diabetes *** constructing CHO cell lines that stably express the human SGLT2 transmembrane protein,along with a fluorescent glucose transporter assay that uses 2-[N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl)amino]2-deoxyglucose(2-NBDG)as a glucose analog,we have developed a nonradioactive,cell-based assay for the discovery and characterization of SGLT2 inhibitors.

关键词： SGLT2 inhibitor NBDG Type 2 diabetes mellitus Kidney

Flavanols from the Camellia sinensis *** and their hypoglycemic and hypolipidemic activities

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2017年第3期7卷 342-346页

作者： Xin Wang Quan Liu Hongbo Zhu Hongqing Wang Jie Kang zhufang shen Ruoyun Chen State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

α-Glucosidase and lipase inhibitors play important roles in the treatment of hyperglycaemia and dyslipidemia. To identify novel naturally occurring inhibitors, a bioactivity-guided phytochemical research was performed on the pu-erh tea. One new flavanol, named(–)-epicatechin-3-O-(Z)-coumarate(1), and 16 known analogs(2–17) were isolated from the aqueous extract of the pu-erh tea. Their structures were determined by spectroscopic and chemical methods. Furthermore, the water extract of pu-erh tea and its fractions exhibited inhibitory activities against α-glucosidases and lipases in vitro;compound 15 showed moderate inhibitory effect against sucrase with an IC_(50) value of 32.5 μmol/L and significant inhibitory effect against maltase with an IC_(50) value of 1.3 μmol/L. Compounds 8, 10, 11 and15 displayed moderate activity against a lipase with IC_(50) values of 16.0, 13.6, 19.8, and 13.3 μmol/L,respectively.

关键词： Camellia sinensis var. assamica Pu-erh tea Flavanol Hypoglycemic Hypolipidemic

Anti-diabetic effects and mechanisms of action of a Chinese herbal medicine preparation JQ-R in vitro and in diabetic KKAy mice

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2017年第4期7卷 461-469页

作者： Quan Liu Shuainan Liu Lihui Gao Sujuan Sun Yi Huan Caina Li Yue Wang Nan Guo zhufang shen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Biomedical Engineering Research Center Kunming Medical UniversityKunming 650500China

Refined-JQ(JQ-R) is a mixture of refined extracts from Coptis chinensis(Ranunculaceae),Astragalus membranaceus(Leguminosae) and Lonicera japonica(Caprifoliaceae), the three major herbs of Jin Qi-Jiang Tang tablet, a traditional Chinese medicine(TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KK^(Ay)mice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid(PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KK^(Ay)mice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase(SOD) and decreased malondialdehyde(MDA) as well as inducible nitric oxide synthase(iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B(NF-κB p65), inhibitor of NF-κB(IκBα), c-Jun N-terminal kinase(JNK1/2) and extracellular-signal-regulated kinases(ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KK^(Ay)mice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.

关键词： TCM Type 2 diabetes mellitus Insulin signalling Inflammation Oxidative stress

GLP-1 Analogue Liraglutide improves Insulin Resistance in Diet-induced Obese Mice:Hyperinsulinemic-Euglycemic Clamp Studies

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

GLP-1 Analogue Liraglutide improves Insulin Resistance in Di...

The application of 2-NBDG as a fluorescent tracer for assessing hepatic glucose production in mice during hyperinsulinemic euglycemic clamp

中华医学会第十二次全国内分泌学学术会议

作者： Juan Li Weigang Zhao Shuainan Liu zhufang shen Department of Endocrinology Key Laboratory of EndocrinologyMinistry of HealthPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical College State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeDiabetes Research Center of Chinese Academy of Medical Sciences

Objective It is widely considered that hyperinsulinemic-euglycemic clamp is the"gold standard"method for assessing insulin sensitivity in *** sought to assess whether GLP-1 analogue liraglutide improve insulin sensitivity in obese mice, and evaluate its effect on the level of adipokine leptin,resistin and adiponectin in serum. Methods Six- to eight-week-old female C57BL/6J mice were fed a standard chow(SC;10%lipids) diet(normal control

关键词：

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2012年第4期2卷 403-410页

作者： Shuainan Liu Quan Liu Sujuan Sun Qian Jiang Jun Peng zhufang shen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeDiabetes Research Center of Chinese Academy of Medical SciencesBeijing 100050China

Methods of performing insulin clamps vary between *** we present a protocol of insulin clamping in conscious mice,with the significant advantage of avoiding multiple surgical catheterizations and non-physiologic metabolism during the induction of *** this technique we also established a new method for measuring hepa tic glucose production(HGP)using a fuorescent D-glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglu-cose(2-NBDG).To prove the reliability and feasibility of this method,whole-body insulin sensitivity was compared between conscious normal ICR mice and diabetic KK^(Ay) mice using the insulin *** and clamp HGP was compared between normal C57 mice and diabetic db/db mice by using the modified clamp with 2-NBDG as a *** glucose infusion rate(GIR),an index of insulin sensitivity,was significantly lower in KKAy mice than normal ICR mice.(6.2±1.3 mg/kg/min vs.31.3±2.9 mg/kg/min,P<0.001).The db/db mice also showed higher basal hepatic glucose production(25.8±2.2 mg/kg/min vs.16.7±2.5 mg/kg/min,P<0.05),higher clamp HGP after insulin suppression(7.3±1.0 mg/kg/min vs.0 mg/kg/min,P<0.001),and lower GIR(71.6±2.8 mg/kg/min vs.15.2±1.6 mg/kg/min,P<0.001)than that obtained with normal C57 *** conclusion,this is the first report of the application of 2-NBDG,rather than isotopic tracers,for the determination of HGP in vivo.

关键词： Conscious mice Hyperinsulinemic euglycemic clamp 2-NBDG Hepatic glucose production

Microbial transformation of lovastatin by Beauveria bassiana

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2012年第3期2卷 300-305页

作者： Lirui Qiao Dan Xie Quan Liu Jianhua Zou zhufang shen Jungui Dai State Key Laboratory of Bioactive Substance and Function of Natural Medicines&Key Laboratory of Biosynthesis of Natural Products Ministry of HealthInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Microbial transformation of lovastatin(1)by resting cells of a filamentous fungus,Beauveria bassiana AS 3.4270,yielded five metabolites(2-6),which were unambiguously characterized by various spectroscopic data *** occurred reactions included hydroxyla-tion,lactone hydrolysis and *** inhibitory effects of all metabolites on the 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA)reductase were *** the five compounds,4 ex hibited comparable inhibitory effect to lovastatin on the HMG-CoA reductase with ICso value of 2.2μM,and inhibitory rate of 81.4%.

关键词： Lovastatin Microbial transformation Beauveria bassiana AS 3.4270 Resting cells HMG-CoA reductase

Novel phenyl-urea derivatives as dual-target ligands that can activate both GK and PPARγ

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2012年第6期2卷 588-597页

作者： Lijian Zhang Kang Tian Yongqiang Li Lei Lei Aifang Qin Lijuan Zhang Hongrui Song Lianchao Huo Lijing Zhang Xiaofeng Jin zhufang shen Zhiqiang Feng School of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China Institute of Materia Medica Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

A series of novel phenyl-urea derivatives which can simultaneously activate gluco kinase(GK)and peroxisome proliferator-activated receptorγ(PPARγ)was designed and prepared,and their activation of GK and PPARγ was *** structure--activity relationships of these compounds are also *** compounds showed potent ability to activate both GK and PPARγ.The possible binding mode of one of these compounds with GK and PPARγ were predicted by molecular docking simulation.

关键词： Type 2 diabetes GK activators PPARγagonists Dual action

Transient Characteristics and Accommodative Current Limiting Strategy for Bidirectional Interlinking Converters in Hybrid AC/DC Microgrids

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

CSEE Journal of Power and Energy Systems 2024年第4期10卷 1575-1588页

作者： Xia shen Zhikang Shuai Wen Huang Chao shen Yang shen Z.John shen College of Electrical and Information Engineering Hunan UniversityChangsha 410082China Department of Electrical and Computer Engineering Illinois Institute of TechnologyChicagoIL 60616 USA

Bidirectional interlinking converter(BIC)is the core equipment in a hybrid AC/DC microgrid connected between AC and DC ***,the variety of control modes and flexible bidirectional power flow complicate the influence of AC faults on BIC itself and on DC sub-grid,which potentially threaten both converter safety and system *** study first investigates AC fault influence on the BIC and DC bus voltage under different BIC control modes and different pre-fault operation states,by developing a mathematical model and equivalent sequence ***,based on the analysis results,a general accommodative current limiting strategy is proposed for BIC without limitations to specific mode or operation *** amplitude is predicted and constrained according to the critical requirements to protect the BIC and relieving the AC fault influence on the DC bus *** with conventional methods,potential current limit failure and distortions under asymmetric faults can also be ***,experiments verify feasibility of the proposed method.

关键词： Bidirectional interlinking converter current limiting fault characteristic hybrid AC/DC microgrid variation/oscillation of DC bus voltage

Rational Solutions of First Order Algebraic Ordinary Differential Equations

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Systems Science & Complexity 2024年第2期37卷 567-580页

作者： FENG Shuang shen Liyong School of Physical and Mathematical Sciences Nanjing Tech UniversityNanjing 211816China School of Mathematical Sciences University of Chinese Academy of SciencesBeijing 100049China

Let f(t,y,y')=∑ _(i=0)^(n )a_(i)(t,y)y'^(i)=0 be an irreducible first order ordinary differential equation with polynomial *** in 1998 proved that there exists a constant C such that every rational solution of f(t,y,y')=0 is of degree not greater than *** show that this degree bound C depends not only on the degrees of f in t,y,y' but also on the coefficients of f viewed as the polynomial in t,y,y'.In this paper,the authors show that if f satisfies deg(f,y)0,then the degree bound C only depends on the degrees of f in t,y,y',and furthermore we present an explicit expression for C in terms of the degrees of f in t,y,y'.

关键词： Degree bound first order AODE height rational solution