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Cystic fibrosis-related diabetes:The unmet need 认领
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作者 Leonardo Pozo Fatimah Bello +1 位作者 Yamely Mendez Salim Surani 《世界糖尿病杂志:英文版(电子版)》 SCIE CAS 2020年第6期213-217,共5页
Cystic fibrosis(CF)is a common autosomal recessive disease.Life expectancy of patients with CF continues to improve mainly driven by the evolving therapies for CF-related organ dysfunction.The prevalence of CF-related... Cystic fibrosis(CF)is a common autosomal recessive disease.Life expectancy of patients with CF continues to improve mainly driven by the evolving therapies for CF-related organ dysfunction.The prevalence of CF-related diabetes(CFRD)increases exponentially as patients’age.Clinical care guidelines for CFRD from 2010,recommend insulin as the mainstay of treatment.Many patients with CFRD may not require exogenous insulin due to the heterogeneity of this clinical entity.Maintenance of euglycemia by enhancing endogenous insulin production,secretion and degradation with novel pharmacological therapies like glucagonlike peptide-1 agonist is an option that remains to be fully explored.As such,the scope of this article will focus on our perspective of glucagon-like peptide-1 receptor agonist in the context of CFRD.Other potential options such as sodiumglucose cotransporter-2 and dipeptidyl peptidase 4 inhibitors and their impact on this patient population is limited and further studies are required. 展开更多
关键词 Cystic fibrosis Cystic fibrosis-related diabetes Cystic fibrosis transmembrane conductance regulator Gastric inhibitory polypeptide Glucagon-like peptide 1 Glucagon-like peptide-1 receptor agonist Dipeptidyl peptidase 4 inhibitors
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Post-transplant diabetes mellitus and preexisting liver disease-a bidirectional relationship affecting treatment and management 认领
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作者 Maja Cigrovski Berkovic Lucija Virovic-Jukic +1 位作者 Ines Bilic-Curcic Anna Mrzljak 《世界胃肠病学杂志:英文版》 SCIE CAS 2020年第21期2740-2757,共18页
Liver cirrhosis and diabetes mellitus(DM)are both common conditions with significant socioeconomic burden and impact on morbidity and mortality.A bidirectional relationship exists between DM and liver cirrhosis regard... Liver cirrhosis and diabetes mellitus(DM)are both common conditions with significant socioeconomic burden and impact on morbidity and mortality.A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications.Type 2 DM(T2DM)is a wellrecognized risk factor for chronic liver disease and vice-versa,DM may develop as a complication of cirrhosis,irrespective of its etiology.Liver transplantation(LT)represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease(NAFLD),which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM.The metabolic risk factors including immunosuppressive drugs,can contribute to persistent or de novo development of DM and NAFLD after LT.T2DM,obesity,cardiovascular morbidities and renal impairment,frequently associated with metabolic syndrome and NAFLD,may have negative impact on short and long-term outcomes following LT.The treatment of DM in the context of chronic liver disease and post-transplant is challenging,but new emerging therapies such as glucagon-like peptide-1 receptor agonists(GLP-1RAs)and sodium–glucose cotransporter 2 inhibitors(SGLT2i)targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management. 展开更多
关键词 Diabetes mellitus Liver transplantation Non-alcoholic fatty liver disease Metabolic syndrome INSULIN-RESISTANCE Glucagon-like peptide-1 receptor agonists Sodium–glucose cotransporter 2 inhibitors
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Is there a role for glucagon-like peptide-1 receptor agonists in the management of diabetic nephropathy? 认领
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作者 Stavroula Veneti Konstantinos Tziomalos 《世界糖尿病杂志:英文版(电子版)》 SCIE CAS 2020年第9期370-373,共4页
Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diab... Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diabetic kidney disease(DKD).GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes mellitus.This beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lowering,anti-inflammatory and antioxidant effects.On the other hand,GLP-1 RAs do not appear to affect the rate of decline of glomerular filtration rate.However,this might be due to the relatively short duration of the trials that evaluated their effects on DKD.Moreover,these trials were not designed nor powered to assess renal outcomes.Given than macrolbuminuria is a strong risk factor for the progression of DKD,it might be expected that GLP-1 RAs will prevent the deterioration in renal function in the long term.Nevertheless,this remains to be shown in appropriately designed randomized controlled trials in patients with DKD. 展开更多
关键词 Diabetic nephropathy Type 2 diabetes mellitus Glucagon-like peptide-1 receptor agonists LIRAGLUTIDE Dulaglutide Semaglutide
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Analysis of long noncoding RNA-associated competing endogenous RNA network in glucagon-like peptide-1 receptor agonist-mediated protection inβcells 认领
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作者 Li-Juan Cui Tao Bai +9 位作者 Lin-Ping Zhi Zhi-Hong Liu Tao Liu Huan Xue Huan-Huan Yang Xiao-Hua Yang Min Zhang Ya-Ru Niu Yun-Feng Liu Yi Zhang 《世界糖尿病杂志:英文版(电子版)》 SCIE CAS 2020年第9期374-390,共17页
BACKGROUND Long noncoding RNAs(lncRNAs)and mRNAs are widely involved in various physiological and pathological processes.The use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)is a novel therapeutic strategy th... BACKGROUND Long noncoding RNAs(lncRNAs)and mRNAs are widely involved in various physiological and pathological processes.The use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)is a novel therapeutic strategy that could promote insulin secretion and decrease the rate ofβ-cell apoptosis in type 2 diabetes mellitus(T2DM)patients.However,the specific lncRNAs and mRNAs and their functions in these processes have not been fully identified and elucidated.AIM To identify the lncRNAs and mRNAs that are involved in the protective effect of GLP-1RA inβcells,and their roles.METHODS Rat gene microarray was used to screen differentially expressed(DE)lncRNAs and mRNAs inβcells treated with geniposide,a GLP-1RA.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to assess the underlying functions of DE mRNAs.Hub mRNAs were filtered using the STRING database and the Cytoscape plugin,CytoHubba.In order to reveal the regulatory relationship between lncRNAs and hub mRNAs,their co-expression network was constructed based on the Pearson coefficient of DE lncRNAs and mRNAs,and competing endogenous RNA(ceRNA)mechanism was explored through miRanda and TargetScan databases.RESULTS We identified 308 DE lncRNAs and 128 DE mRNAs with a fold change filter of≥1.5 and P value<0.05.GO and KEGG pathway enrichment analyses indicated that the most enriched terms were G-protein coupled receptor signaling pathway,inflammatory response,calcium signaling pathway,positive regulation of cell proliferation,and ERK1 and ERK2 cascade.Pomc,Htr2a,and Agtr1a were screened as hub mRNAs using the STRING database and the Cytoscape plugin,CytoHubba.This result was further verified using SwissTargetPrediction tool.Through the co-expression network and competing endogenous(ceRNA)mechanism,we identified seven lncRNAs(NONRATT027738,NONRATT027888,NONRATT030038,etc.)co-expressed with the three hub mRNAs(Pomc,Htr2a,and Agtr1a)based on the Pearson coefficient of the expression levels.These lncRNAs regula 展开更多
关键词 Type 2 diabetes βcell Long noncoding RNA Competing endogenous RNA Co-expression analysis Glucagon-like peptide-1 receptor agonist
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Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update 认领
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作者 Areti Sofogianni Athanasios Filippidis +2 位作者 Lampros Chrysavgis Konstantinos Tziomalos Evangelos Cholongitas 《世界肝病学杂志:英文版(电子版)》 CAS 2020年第8期493-505,共13页
Non-alcoholic fatty liver disease(NAFLD)is the predominant cause of chronic liver disease worldwide.NAFLD progresses in some cases to non-alcoholic steatohepatitis(NASH),which is characterized,in addition to liver fat... Non-alcoholic fatty liver disease(NAFLD)is the predominant cause of chronic liver disease worldwide.NAFLD progresses in some cases to non-alcoholic steatohepatitis(NASH),which is characterized,in addition to liver fat deposition,by hepatocyte ballooning,inflammation and liver fibrosis,and in some cases may lead to hepatocellular carcinoma.NAFLD prevalence increases along with the rising incidence of type 2 diabetes mellitus(T2DM).Currently,lifestyle interventions and weight loss are used as the major therapeutic strategy in the vast majority of patients with NAFLD.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are used in the management of T2DM and do not have major side effects like hypoglycemia.In patients with NAFLD,the GLP-1 receptor production is down-regulated.Recently,several animal and human studies have emphasized the role of GLP-1RAs in ameliorating liver fat accumulation,alleviating the inflammatory environment and preventing NAFLD progression to NASH.In this review,we summarize the updated literature data on the beneficial effects of GLP-1RAs in NAFLD/NASH.Finally,as GLP-1RAs seem to be an attractive therapeutic option for T2DM patients with concomitant NAFLD,we discuss whether GLP-1RAs should represent the first line pharmacotherapy for these patients. 展开更多
关键词 Glucagon-like peptide-1 receptor agonists Non-alcoholic fatty liver disease Type 2 diabetes mellitus Clinical studies Fatty liver Animal studies
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Effects of Incretin-based Therapies on Weight-related Indicators among Patients with Type 2 Diabetes: A Network Meta-analysis 认领
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作者 XU Lu YU Shu Qing +10 位作者 GAO Le HUANG Yi WU Shan Shan YANG Jun SUN Yi Xin YANG Zhi Rong CHAI San Bao ZHANG Yuan JI Li Nong SUN Feng ZHAN Si Yan 《生物医学与环境科学:英文版》 SCIE CAS CSCD 2020年第1期37-47,共11页
Objective To evaluate the effects of incretin-based therapies on body weight as the primary outcome,as well as on body mass index(BMI)and waist circumference(WC)as secondary outcomes.Methods Databases including Medlin... Objective To evaluate the effects of incretin-based therapies on body weight as the primary outcome,as well as on body mass index(BMI)and waist circumference(WC)as secondary outcomes.Methods Databases including Medline,Embase,the Cochrane Library,and clinicaltrials.gov(www.clinicaltrials.gov)were searched for randomized controlled trials(RCTs).Standard pairwise meta-analysis and network meta-analysis(NMA)were both carried out.The risk of bias(ROB)tool recommended by the Cochrane handbook was used to assess the quality of studies.Subgroup analysis,sensitivity analysis,meta-regression,and quality evaluation based on the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)were also performed.Results A total of 292 trials were included in this study.Compared with placebo,dipeptidyl-peptidase IV inhibitors(DPP-4 Is)increased weight slightly by 0.31 kg[95%confidence interval(CI):0.05,0.58]and had negligible effects on BMI and WC.Compared with placebo,glucagon-like peptide-1 receptor agonists(GLP-1 RAs)lowered weight,BMI,and WC by-1.34 kg(95%CI:-1.60,-1.09),-1.10 kg/m2(95%CI:-1.42,-0.78),and-1.28 cm(95%CI:-1.69,-0.86),respectively.Conclusion GLP-1 RAs were more effective than DPP-4 Is in lowering the three indicators.Overall,the effects of GLP-1 RAs on weight,BMI,and WC were favorable. 展开更多
关键词 BODY mass index BODY WEIGHT Diabetes mellitus Dipeptidyl-peptidase IV inhibitors Glucagon-like peptide-1 receptor AGONISTS Network meta-analysis WAIST CIRCUMFERENCE
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高糖对肝脏胰高血糖素受体的表达及作用影响 认领 被引量:1
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作者 刘梦丹 冀琳琳 +4 位作者 叶阳 祝超瑜 肖元元 高清歌 魏丽 《中国医药导报》 CAS 2019年第22期12-16,F0004共6页
目的观察db/db小鼠肝组织和高糖对待的肝癌细胞株HepG2细胞中胰高血糖素受体(GCGR)的表达及作用的变化。方法db/db小鼠和对照小鼠均进行腹腔注射葡萄糖耐量试验(IPGTT)和腹腔注射胰岛素耐量试验(IPITT),收集两组小鼠的血液进行生化指标... 目的观察db/db小鼠肝组织和高糖对待的肝癌细胞株HepG2细胞中胰高血糖素受体(GCGR)的表达及作用的变化。方法db/db小鼠和对照小鼠均进行腹腔注射葡萄糖耐量试验(IPGTT)和腹腔注射胰岛素耐量试验(IPITT),收集两组小鼠的血液进行生化指标检测;采用Westernblot或免疫组化法检测两组小鼠肝脏中GCGR、蛋白激酶A(PKA)、磷酸化蛋白激酶A(p-PKA)的表达情况。采用Westernblot法检测在无胰高血糖素(GLN)刺激下,不同糖浓度或不同时间梯度高糖(30mmol/L)处理的HepG2细胞GCGR的表达情况,以及在GLN刺激下,不同时间梯度高糖处理的HepG2细胞GCGR、PKA、p-PKA蛋白的表达情况。结果与对照小鼠比较,db/db小鼠肝脏GCGR表达增加,而PKA磷酸化水平下降(P<0.05或P<0.01)。HepG2细胞的GCGR蛋白表达水平随葡萄糖浓度增加而升高,随高糖作用时间延长先下降后升高(均P<0.01)。GLN刺激下,随着高糖对待时间的增加,GCGR蛋白表达水平逐渐升高(均P<0.01);p-PKA/PKA水平则较对照组(0h)降低(P<0.05或P<0.01)。结论慢性高糖可增加肝脏GCGR的表达,并导致肝脏胰高血糖素抵抗。 展开更多
关键词 胰高血糖素受体 胰高血糖素抵抗 糖尿病 DB/DB小鼠 HEPG2细胞
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新型抗2型糖尿病靶点药物的研究进展 认领
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作者 张少坤 熊丽娟 +2 位作者 杨尊华 金一 房元英 《中国新药杂志》 CAS CSCD 北大核心 2019年第14期1718-1726,共9页
糖尿病是一种血液中有异常高水平葡萄糖的慢性代谢性疾病,其中2型糖尿病患者高达90%。目前糖尿病的患病率在全球范围内持续上升,尤其是在发展中国家。对于糖尿病的治疗有多种药物,针对α-葡萄糖苷酶、胰高血糖素样肽-1(GLP-1)受体、二... 糖尿病是一种血液中有异常高水平葡萄糖的慢性代谢性疾病,其中2型糖尿病患者高达90%。目前糖尿病的患病率在全球范围内持续上升,尤其是在发展中国家。对于糖尿病的治疗有多种药物,针对α-葡萄糖苷酶、胰高血糖素样肽-1(GLP-1)受体、二肽基肽酶IV(DPP-4)和钠-葡萄糖协同转运蛋白2(SGLT2)等靶点的药物已经上市,同时一些新的靶点如G蛋白偶联受体119(GPR119)、蛋白酪氨酸磷酸酶-1B(PTP1B)、胰高血糖素受体(GCGr)、G蛋白偶联受体40(GPR40)、糖原合成酶激酶3(GSK-3)、糖原磷酸化酶(GP)、11β-羟基类固醇脱氢酶1(11β-HSD1)等也对开发抗糖尿病药物具有重要的价值。这些新靶点为抗糖尿病药物的研发提供了更多的方向,对治疗糖尿病具有重大的意义。 展开更多
关键词 2型糖尿病 G蛋白偶联受体119 G蛋白偶联受体40 胰高血糖素受体 糖原磷酸化酶
Development of therapeutic options on type 2 diabetes in years: Glucagon-like peptide-1 receptor agonist’s role intreatment;from the past to future 认领
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作者 Hakan Dogruel Mustafa Kemal Balci 《世界糖尿病杂志:英文版(电子版)》 2019年第8期446-453,共8页
Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia.Type 2 diabetes (T2DM) accounting for 90% of cases globally.The worldwide prevalence of DM is rising dramatically over the last deca... Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia.Type 2 diabetes (T2DM) accounting for 90% of cases globally.The worldwide prevalence of DM is rising dramatically over the last decades,from 30 million cases in 1985 to 382 million cases in 2013.It’s estimated that 451 million people had diabetes in 2017.As the pathophysiology was understood over the years,treatment options for diabetes increased.Incretin-based therapy is one of them.Glucagon-like peptide-1 receptor agonist (GLP-1 RA) not only significantly lower glucose level with minimal risk of hypoglycemia but also,they have an important advantage in themanagement of cardiovascular risk and obesity.Thus,we will review here GLP-1 RAsrole in the treatment of diabetes. 展开更多
关键词 Incretin-basedtherapy INCRETIN MIMETICS Glucagon-like peptide-1 receptor AGONIST Dipeptidyl peptidase-4 inhibitor
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Liraglutide Ameliorates Hyperhomocysteinemia-Induced Alzheimer-Like Pathology and Memory Deficits in Rats via Multi-molecular Targeting 认领
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作者 Yao Zhang Jia-Zhao Xie +5 位作者 Xiang-Yang Xu Jun Hu Teng Xu Si Jin Shao-Juan Yang Jian-Zhi Wang 《神经科学通报:英文版》 SCIE CAS CSCD 2019年第4期724-734,共11页
Hyperhomocysteinemia(Hhcy)is an independent risk factor for Alzheimer's disease(AD),and insulinresistance is commonly seen in patients with Hhcy.Liraglutide(Lir),a glucagon-like peptide that increases the secretio... Hyperhomocysteinemia(Hhcy)is an independent risk factor for Alzheimer's disease(AD),and insulinresistance is commonly seen in patients with Hhcy.Liraglutide(Lir),a glucagon-like peptide that increases the secretion and sensitivity of insulin,has a neurotrophic or neuroprotective effect.However,it is not known whether Lir ameliorates the AD-like pathology and memory deficit induced by Hhcy.By vena caudalis injection of homocysteine to produce the Hhcy model in rats,we found here that simultaneous administration of Lir for 2 weeks ameliorated the Hhcy-induced memory deficit,along with increased density of dendritic spines and up-regulation of synaptic proteins.Lir also attenuated the Hhcy-induced tau hyperphosphorylation and Aβ overproduction,and the molecular mechanisms involved the restoration of protein phosphatase-2 A activity and inhibition of β-and γ-secretases.Phosphorylated insulin receptor substrate-1 also decreased after treatment with Lir.Our data reveal that Lir improves the Hhcy-induced AD-like spatial memory deficit and the mechanisms involve the modulation of insulinresistance and the pathways generating abnormal tau and Aβ. 展开更多
关键词 LIRAGLUTIDE HYPERHOMOCYSTEINEMIA Glucagon-like peptide-1 receptor Tau Β-AMYLOID
Prevention of macrovascular complications in patients with type 2 diabetes mellitus: Review of cardiovascular safety and efficacy of newer diabetes medications 认领
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作者 Ravi Kant Kashif M Munir +1 位作者 Arshpreet Kaur Vipin Verma 《世界糖尿病杂志:英文版(电子版)》 2019年第6期324-332,共9页
Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized cont... Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized controversy surrounding cardiovascular (CV) safety of rosiglitazone resulted in major changes in United States Food and Drug Administration policy in 2008 regarding approval process of new antidiabetic medications, which has resulted in revolutionary data from several large CV outcome trials over the last few years. All drugs in glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor classes have shown to be CV safe with heterogeneous results on CV efficacy. Given twofold higher CV disease mortality in patients with DM than without DM, GLP-1 RAs and SGLT-2-inhibitors are important additions to clinician’s armamentarium and should be second line-therapy particularly in patients with T2DM and established atherosclerotic CV disease or high risks for CV disease. Abundance of data and heterogeneity in CV outcome trials results can make it difficult for clinicians, particularly primary care physicians, to stay updated with all the recent evidence. The scope of this comprehensive review will focus on all major CV outcome studies evaluating CV safety and efficacy of GLP-1 RAs and SGLT-2 inhibitors. 展开更多
关键词 Newer antidiabetic MEDICATIONS Glucagon-like peptide-1 receptor agonist Sodium-glucose cotransporter-2 inhibitors Type 2 DIABETES MELLITUS Macrovascular complications CARDIOVASCULAR outcome trials Major CARDIOVASCULAR events HEART failure PREVENTION of HEART disease
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Advances in reducing cardiovascular risk in the management of patients with type 2 diabetes mellitus 认领
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作者 Ying Hu 《慢性疾病与转化医学:英文版》 CSCD 2019年第1期25-36,共12页
Treatment intended to lower cardiovascular (CV) risk in patients with diabetes has always been a primary goal of diabetes treatment. Due to the subdued effects of reducing hemoglobin A1c (HbA1c) on macrovascular compl... Treatment intended to lower cardiovascular (CV) risk in patients with diabetes has always been a primary goal of diabetes treatment. Due to the subdued effects of reducing hemoglobin A1c (HbA1c) on macrovascular complications, controlling other CV risk factors such as hypertension and hyperlipidemia instead of hyperglycemia has been the mainstay treatment to improve CV outcome in patients with type 2 diabetes mellitus (T2DM) until recent years. This review is intended to summarize and compare the results from the available cardiovascular outcome trials (CVOTs) for the two classes of glucose lowering drug: sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). The results including the EMPA-REG, CANVAS program and DECLARE-TIMI 58 trials for SGLT2i, and the ELIXA, LEADER, SUSTAIN-6, EXSCEL and HARMONY trials for GLP-1 RA were summarized. The potential mechanisms of these CV beneficial effects and the optimal CV risk reduction treatment in patients with T2DM based on patient risk stratification and evidence from these CVOTs in real-world setting were discussed. 展开更多
关键词 Type 2 diabetes MELLITUS (T2DM) CARDIOVASCULAR risk CARDIOVASCULAR outcome trial (CVOT) Sodium-glucose co-transporter 2 inhibitor (SGLT2i) Glucagon-like peptide-1 receptor AGONIST (GLP-1 RA)
抗体药物在糖尿病治疗应用的研究进展 认领 被引量:1
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作者 郑清梅 王亚端 +3 位作者 谭双羽 陈晓乐 张南文 阳菊华 《中国临床药理学杂志》 CAS CSCD 北大核心 2019年第8期812-815,共4页
糖尿病是一种慢性高血糖的代谢性疾病。其发病率高、危害大,极大加重家庭的负担。现阶段,主要以胰岛素或者口服降糖药治疗为主,但血糖控制效果不佳,易引起低血糖等常见副作用和各种并发症。抗体药物具有高选择性和高治疗指数,是目前药... 糖尿病是一种慢性高血糖的代谢性疾病。其发病率高、危害大,极大加重家庭的负担。现阶段,主要以胰岛素或者口服降糖药治疗为主,但血糖控制效果不佳,易引起低血糖等常见副作用和各种并发症。抗体药物具有高选择性和高治疗指数,是目前药物研究的热门方向。本文从T细胞、B淋巴细胞、胰高血糖素受体、血管内皮生长因子不同靶点论述了抗体药物在糖尿病治疗应用的研究进展,以期能为糖尿病的治疗提供参考依据。 展开更多
关键词 抗体药物 T细胞 B淋巴细胞 胰高血糖素受体 血管内皮生长因子
Glucagon-like peptide-1 receptor gene polymorphism is associated with fat mass in Chinese nuclear families with male offspring 认领
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作者 Shoukui Xiang Luyue Qi +5 位作者 Fei Zhao Wenjie Wang Xiaoya Zhang Yunqiu Hu Fei Hua Zhenlin Zhang 《生物化学与生物物理学报:英文版》 SCIE CAS CSCD 2019年第5期545-547,共3页
Obesity is a serious and growing worldwide health threat associated with increased risk of Type 2 diabetes,hypertension,dyslipidemia,cardiovascular disease,and several forms of cancers[1].It is a complex disease under... Obesity is a serious and growing worldwide health threat associated with increased risk of Type 2 diabetes,hypertension,dyslipidemia,cardiovascular disease,and several forms of cancers[1].It is a complex disease under strong genetic control,and a number of genetic variants for obesity have been identified[2].However,the identified loci explain only a small proportion of the heritability for obesity,suggesting that more associated variants remain to be discovered.Glucagon-like peptide-1(GLP-1)is a potent glucose-dependent insulinotropic gut hormone that is secreted from enteroendocrine L cells of the terminal ileum.In addition to its insulinotropic effects,GLP-1 prevents fat accumulation through various mechanisms[3].GLP-1 exerts its action through the GLP-1 receptor(GLP-1R)which has a wide tissue distribution including adipose tissue.Previous studies have shown that single-nucleotide polymorphisms(SNPs)in the GLP-1R gene may alter binding affinity for GLP-1 and intracellular signaling after hormone-receptor binding[4,5]. 展开更多
关键词 Glucagon-like RECEPTOR gene POLYMORPHISM MALE OFFSPRING
Metabolic and hepatic effects of liraglutide,obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis 认领
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作者 Kirstine S Tolbol Maria NB Kristiansen +6 位作者 Henrik H Hansen Sanne S Veidal Kristoffer TG Rigbolt Matthew P Gillum Jacob Jelsing Niels Vrang Michael Feigh 《世界胃肠病学杂志:英文版》 SCIE CAS 2018年第2期179-194,共16页
AIM To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis(NASH)in obese mouse models of biopsy-confirmed NASH.METHODS Male wild-type C57BL/6J mice(DIO-NASH)and Lepob/ob... AIM To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis(NASH)in obese mouse models of biopsy-confirmed NASH.METHODS Male wild-type C57BL/6J mice(DIO-NASH)and Lepob/ob(ob/ob-NASH)mice were fed a diet high in trans-fat(40%),fructose(20%)and cholesterol(2%)for 30 and 21 wk,respectively.Prior to treatment,all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis,using the nonalcoholic fatty liver disease activity score(NAS)and fibrosis staging system.The mice were kept on the diet and received vehicle,liraglutide(0.2 mg/kg,SC,BID),obeticholic acid(OCA,30 mg/kg PO,QD),or elafibranor(30 mg/kg PO,QD)for eight weeks.Within-subject comparisons were performed on changes in steatosis,inflammation,ballooning degeneration,and fibrosis scores.In addition,compound effects were evaluated by quantitative liver histology,including percent fractional area of liver fat,galectin-3,and collagen 1a1.RESULTS Liraglutide and elafibranor,but not OCA,reduced body weight in both models.Liraglutide improved steatosis scores in DIO-NASH mice only.Elafibranor and OCA reduced histopathological scores of hepatic steatosis and inflammation in both models,but only elafibranor reduced fibrosis severity.Liraglutide and OCA reduced total liver fat,collagen 1a1,and galectin-3 content,driven by significant reductions in liver weight.The individual drug effects on NASH histological endpoints were supported by global gene expression(RNA sequencing)and liver lipid biochemistry.CONCLUSION DIO-NASH and ob/ob-NASH mouse models show distinct treatment effects of liraglutide,OCA,and elafibranor,being in general agreement with corresponding findings in clinical trials for NASH.The present data therefore further supports the clinical translatability and utility of DIO-NASH and ob/ob-NASH mouse models of NASH for probing the therapeutic efficacy of compounds in preclinical drug development for NASH. 展开更多
关键词 Nonalcoholic steatohepatitis Disease models Pathology Fibrosis Liver BIOPSY TRANSCRIPTOMICS PHARMACODYNAMICS Glucagon-like peptide-1 RECEPTOR PEROXISOME proliferator-activated RECEPTOR Farnesoid X RECEPTOR
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Effects of glucose-lowering agents on cardiorespiratory fitness 认领
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作者 Hidetaka Hamasaki 《世界糖尿病杂志:英文版(电子版)》 2018年第12期230-238,共9页
Exercise therapy is essential for the management of type 2 diabetes(T2D).However,patients with T2D show lower physical activity and reduced cardiorespiratory fitness than healthy individuals.It would be ideal for clin... Exercise therapy is essential for the management of type 2 diabetes(T2D).However,patients with T2D show lower physical activity and reduced cardiorespiratory fitness than healthy individuals.It would be ideal for clinicians to co-prescribe glucose-lowering agents that improve cardiorespiratory fitness or exercise capacity in conjunction with exercise therapy.Metformin does not improve cardiorespiratory fitness and may attenuate any beneficial effect of exercise in patients with T2D.In contrast,thiazolidinediones appear to improve cardiorespiratory fitness in patients with T2D.Although evidence is limited,sodium–glucose cotransporter 2(SGLT2)inhibitors may improve cardiorespiratory fitness in patients with heart failure,and the effect of glucagon-like peptide-1(GLP-1)receptor agonists on cardiorespiratory fitness is controversial.Recent clinical trials have shown that both SGLT2 inhibitors and GLP-1 receptor agonists exert a favorable effect on cardiovascular disease.It becomes more important to choose drugs that have beneficial effects on the cardiovascular system beyond glucose-lowering effects.Further studies are warranted to determine an ideal glucose-lowering agent combined with exercise therapy for the treatment of T2D. 展开更多
关键词 Type 2 diabetes Glucagon-like peptide l receptor AGONIST CARDIORESPIRATORY fitness Exercise capacity METFORMIN THIAZOLIDINEDIONE Sodium-glucose COTRANSPORTER 2 inhibitors
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胰升糖素受体单克隆抗体:糖尿病药物治疗的新方向 认领
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作者 郎杉 魏蕊 洪天配 《中华内分泌代谢杂志》 CAS CSCD 北大核心 2018年第12期1052-1056,共5页
胰升糖素通过与肝脏、胰腺等组织中的胰升糖素受体(GCGR)结合,从而调节糖脂代谢、体重等。在糖尿病状态下,胰升糖素分泌不适当增高导致肝糖输出增加,而阻断GCGR可恢复血糖的稳态。阻断GCGR的方法包括GCGR单克隆抗体(单抗)、拮抗剂、反... 胰升糖素通过与肝脏、胰腺等组织中的胰升糖素受体(GCGR)结合,从而调节糖脂代谢、体重等。在糖尿病状态下,胰升糖素分泌不适当增高导致肝糖输出增加,而阻断GCGR可恢复血糖的稳态。阻断GCGR的方法包括GCGR单克隆抗体(单抗)、拮抗剂、反义寡核苷酸及基因敲除。GCGR单抗可特异性阻断胰升糖素的作用,其在动物实验和临床研究中均被证实能够有效控制血糖,同时不良反应较轻微。因此,GCGR信号与糖尿病的病理生理过程密切相关,GCGR单抗为糖尿病的治疗提供了新的策略。 展开更多
关键词 胰升糖素受体 抗体 单克隆 糖尿病
14—3—3β蛋白介导胰高血糖素作用下糖异生的特点及机制 认领
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作者 冯丽帅 王倩倩 +2 位作者 马旭 王建波 魏丽 《医学研究杂志》 2017年第3期36-38,47共4页
目的分别观察胰高血糖素在空质粒转染组和14—3—3β蛋白过表达组对HepG2细胞糖异生的影响,并对14—3—3β蛋白介导此现象出现的可能原因初步探讨。方法对转染空质粒或14—3—3β质粒低糖培养基培养的HepG2细胞分别在有无胰高血糖素作... 目的分别观察胰高血糖素在空质粒转染组和14—3—3β蛋白过表达组对HepG2细胞糖异生的影响,并对14—3—3β蛋白介导此现象出现的可能原因初步探讨。方法对转染空质粒或14—3—3β质粒低糖培养基培养的HepG2细胞分别在有无胰高血糖素作用下,进行培养基中葡萄糖产量的测定并观察糖异生关键酶蛋白表达量的变化;用免疫共沉淀的方法判定稳定转染胰高血糖素受体的293细胞在胰高血糖素对待下,14—3—3β蛋白与胰高血糖素受体结合的变化。结果在未加及加入胰高血糖素对待下,14—3—3β转染组与空质粒对照组相比葡萄糖产量降低(P均〈0.05);糖异生关键酶表达量降低(P均〈0.05);免疫共沉淀显示胰高血糖素受体、14—3—3β蛋白与碳水化合物反应元件三者处于结合状态,且在胰高血糖素作用下14—3—3β蛋白与胰高血糖素受体结合减少而与碳水化合物反应元件结合增多(P均〈0.05)。结论过表达14—3—3β蛋白可起到抑制胰高血糖素的糖异生作用且这种现象发生的原因可能与其同碳水化合物反应元件间的相互作用及产生的后续效应有关。 展开更多
关键词 胰高血糖素 胰高血糖素受体 14—3—3β蛋白 碳水化合物反应元件
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Highly efficient detection of insulinotropic action of glucagon via GLP-1 receptor in mice pancreatic beta-cell with a novel perfusion microchip 认领
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作者 Li-Dan Hu Yu-Lin Zhang +2 位作者 Hong Wang Xing-Yue Peng Yi Wang 《中国化学快报:英文版》 SCIE CAS CSCD 2016年第7期1027-1031,共5页
Glucagon exhibits insulinotropic ability by activating cAMP through glucagon or glucagon-like peptide-1(GLP-1) receptors.To investigate the mechanism of endogenous and exogenous glucagon on insulin release,we studied ... Glucagon exhibits insulinotropic ability by activating cAMP through glucagon or glucagon-like peptide-1(GLP-1) receptors.To investigate the mechanism of endogenous and exogenous glucagon on insulin release,we studied the receptor selectivity on pancreatic islet beta-cells by switching the glucose concentration from 20 mmol/L to 0 mmol/L To measure the exact temporal relationship between glucagon and insulin release,we developed a quick,small volume,multi-channel polydimethylsiloxane(PDMS) microchip.At 0 mmol/L glucose,we observed an insulinotropic effect in both INS-1 cells and islets.Meanwhile,we observed a 63 ± 6.27 s delay of endogenous glucagon-induced insulin release.After treatment with glucagon and GLP-1 receptor antagonists,we found that endogenous glucagon utilized the glucagon receptor,whereas exogenous glucagon primarily utilized the GLP-1 receptor to promote insulin secretion.The microchip can also be used to describe the 'glucagonocentric' vision of diabetes pathophysiology.Taken together,the insulinotropic mechanism of different receptors should be taken into account in clinical treatments. 展开更多
关键词 胰高血糖素样肽-1 胰岛素分泌 受体拮抗剂 GLP-1 胰腺Β细胞 微芯片 聚二甲基硅氧烷 葡萄糖浓度
肝脏脂肪变对胰高血糖素受体的表达影响 认领 被引量:1
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作者 王倩倩 肖元元 +6 位作者 祝超瑜 魏燕燕 李旭 张明亮 韩峻峰 魏丽 贾伟平 《医学研究杂志》 2016年第9期33-38,共6页
摘要目的观察胰高血糖素受体(GCGR)在ob/ob小鼠肝组织以及肝癌细胞株HepG,细胞脂肪变后表达变化。方法分别检测10周龄的雄性ob/ob小鼠和同窝野生对照小鼠的体重、肝功、血糖、血脂以及胰岛素等指标,用荧光定量PCR方法、Westernblo... 摘要目的观察胰高血糖素受体(GCGR)在ob/ob小鼠肝组织以及肝癌细胞株HepG,细胞脂肪变后表达变化。方法分别检测10周龄的雄性ob/ob小鼠和同窝野生对照小鼠的体重、肝功、血糖、血脂以及胰岛素等指标,用荧光定量PCR方法、Westernblot法和免疫组化分别检测两组鼠肝脏中gcgr基因、蛋白表达的差异以及定位情况。不同浓度油酸处理HepG,细胞,油红0染色观察HepG,细胞脂肪病变程度,QPCR法和Westernblot法检测细胞gcgrmRNA和蛋白的表达变化。结果GCGR广泛表达于多种组织,以肝脏表达较多,ob/ob小鼠呈现明显的脂肪肝性病变,且免疫组化结果发现,ob/ob小鼠与正常对照小鼠相比,肝脏中GCGR表达减少;mRNA表达水平分别为0.709±0.174vs1.000±0.000,与对照组比较,差异有统计学意义(P〈0.05);蛋白表达水平分别为0.761±0.211vs1.200±0.346,与对照组比较,差异有统计学意义(P〈0.05)。不同浓度梯度油酸处理HepG,细胞,其GCGRmRNA和蛋白水平表达随油酸浓度增加而逐渐降低,差异有统计学意义(P〈0.05)。结论肝脏脂肪性病变降低了肝脏GCGR表达水平,从而可能影响肝脏的糖脂代谢。 展开更多
关键词 胰高血糖素受体 非酒精性脂肪肝 糖尿病 ob/ob小鼠HepG2细胞
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