沙格列汀的作用机制课件

onglyza沙格列汀的作用机制onglyza1肠促胰岛激素简史hanza1986证实了2019-DPP-4被1932-首次确1966-首次描长促胰岛素在确定为一种灭活定肠促胰岛素3述DPP462型糖尿病患GIP和GLP1的者中的作用酶9.101902-首次观察1964-证实仓促1973-GIP被确1987-GLP-1到藏到对胰岛分胰岛素效应定为一种人类长被确定为一种泌的影响1,214,5促胰岛素1人类长促胰岛素2.B923.LaBarreJ.BullAcadRMedBelg.1932:120:620-634GG.Histochemle,1966;7(3):197-20ology.2019:1363385-3596DeaconCFetal.JClinEndocrinolMetab,2019:80:952.957.肠促胰岛激素简史2与注边相比讓增强了细胞反0Hy2a与静脉注射葡萄糖相比,口服葡萄糖后,患者的血清C肽水平更高,由此证实了肠促胰素效应口服面糖净脉注射物肠促胰紊效应时间(分钟)时间(分钟平均±SEn=5;P≤0.05:0102=杷翰注时间检测区名健序对照受试者口服俪犊(50g)和脉注射物的反应Nauckj,cinEndocrinolmetab.1986:63-492-8与注边相比讓增强了细胞反0Hy2a32型糖尿病患者肠促胰岛素效应减0nmza非糖尿病组(n=8)2型糖尿病组(n=14)肠促胰岛素效应彐40120Time(min)Time(min)口服葡萄糖静脉注射葡莓糖2型糖尿病患者肠促胰岛素效应减0nmza4RoleofIncretinSysteminGlucoseHomeostasishanzaGlucose-Glucoseinsulin(GLP-1&GIPFPancreasReleaseofpcel→GitracactiveincretinGLP-1GIPactivates(GLP-1GLP-1&GIPAdaptedfromDruckerDJ.CellMetab.2019:3:153-65RoleofIncretinSysteminGlu5GLP1和GIP是两类主要的肠促胰素0nzaGLP-1GIP(胰高糖素样肽-1)(葡萄糖依赖的促胰岛素释放多肽)主要合成部位L细胞K细胞(回肠和结肠)什十二指肠和空肠)2型糖尿病患者中分泌餐后胰高糖素↓食物摄入延缓胃排空促进β细胞增殖是是是是是是否否否否是是促进胰岛素生物合成DruckerD].DiabetesCare.2019:26:2929-2940.GLP1和GIP是两类主要的肠促胰素0nza6TheIncretinEffectisReducedinType2DiabeteshanzaResponsestoglucoseloadintype2diabeticsandhealthysubjectsaOralglucose(50g)Ivglucose(variable)Controlsubjects(N=8)Type2diabeticpatients(N=14)"Ps0.05totherespectivevalueaftertheoralloadTime(min)Time(min)00042Responsestoanoralglucoseloadof50gandintravenousglucoseinfusionweremeasuredin14type2diabeticpatientsand8healthycontrolAdaptedfromNauckM,etal.Diabetologia.1986;29:46-52TheIncretinEffectisReduced7IncretinhormonechangeshanzaGLP-1(pmol/L)Time(minutes)Inpatientswithtype2diabetes,levelsofGLP-1releasedinresponsetoglucosearereducedandglPactivityisdecreasedIncretinhormonechanges8ContinuousInfusionofGLP-1DecreasesFastingGlucoseaswellasHbA1chanzaComparedtosaline,patientstreatedwithGLP-1showedfastingand8-hourmeanplasmaglucosethatwasdecreasedby4.3mmouand5.5mmol/(P<00001),andHbA,cthatwasdecreasedby1.3%(P=0.003)Patientsassignedsaline(N=9PatientsassignedGLP-1(N=10)aWeekaWeek1三AdaptedfromZanderM,etal.Lancet.2019:359(9309):824-30.ContinuousInfusionofGLP-1D9ExogenousGlucose-DependentInsulinotropicPolypeptideWorsensPostprandialHyperglycaemiainType2DiabeteshanzaWhencomparedwithplacebo,exogenousGIPinfusionnotonlydidnotlowerpostprandialglucosebutfurtherworsenedhyperglycaemiaduringlatepostprandialperiod(120-360min)inpatientswithtype2diabetes(N=22)ChangesininsulinChangesinglucosePlaceboETime(min)P<0.05vsplaceboTime(min)GlPgivenatsupraphysiologicallevelsstillhasanearlyshort-livedinsulinotropiceffectintype2diabetesAdaptedfromChiaCw,etal.Diabetes.2009:58(6):1342-9ExogenousGlucose-DependentIn10沙格列汀的作用机制课件11沙格列汀的作用机制课件12沙格列汀的作用机制课件13沙格列汀的作用机制课件14沙格列汀的作用机制课件15沙格列汀的作用机制课件16沙格列汀的作用机制课件17沙格列汀的作用机制课件18沙格列汀的作用机制课件19沙格列汀的作用机制课件20沙格列汀的作用机制课件21沙格列汀的作用机制课件22沙格列汀的作用机制课件23沙格列汀的作用机制课件24沙格列汀的作用机制课件25沙格列汀的作用机制课件26沙格列汀的作用机制课件27沙格列汀的作用机制课件28沙格列汀的作用机制课件29沙格列汀的作用机制课件30沙格列汀的作用机制课件31沙格列汀的作用机制课件32沙格列汀的作用机制课件33沙格列汀的作用机制课件34沙格列汀的作用机制课件35沙格列汀的作用机制课件36沙格列汀的作用机制课件37沙格列汀的作用机制课件38沙格列汀的作用机制课件39沙格列汀的作用机制课件40onglyza沙格列汀的作用机制onglyza41肠促胰岛激素简史hanza1986证实了2019-DPP-4被1932-首次确1966-首次描长促胰岛素在确定为一种灭活定肠促胰岛素3述DPP462型糖尿病患GIP和GLP1的者中的作用酶9.101902-首次观察1964-证实仓促1973-GIP被确1987-GLP-1到藏到对胰岛分胰岛素效应定为一种人类长被确定为一种泌的影响1,214,5促胰岛素1人类长促胰岛素2.B923.LaBarreJ.BullAcadRMedBelg.1932:120:620-634GG.Histochemle,1966;7(3):197-20ology.2019:1363385-3596DeaconCFetal.JClinEndocrinolMetab,2019:80:952.957.肠促胰岛激素简史42与注边相比讓增强了细胞反0Hy2a与静脉注射葡萄糖相比,口服葡萄糖后,患者的血清C肽水平更高,由此证实了肠促胰素效应口服面糖净脉注射物肠促胰紊效应时间(分钟)时间(分钟平均±SEn=5;P≤0.05:0102=杷翰注时间检测区名健序对照受试者口服俪犊(50g)和脉注射物的反应Nauckj,cinEndocrinolmetab.1986:63-492-8与注边相比讓增强了细胞反0Hy2a432型糖尿病患者肠促胰岛素效应减0nmza非糖尿病组(n=8)2型糖尿病组(n=14)肠促胰岛素效应彐40120Time(min)Time(min)口服葡萄糖静脉注射葡莓糖2型糖尿病患者肠促胰岛素效应减0nmza44RoleofIncretinSysteminGlucoseHomeostasishanzaGlucose-Glucoseinsulin(GLP-1&GIPFPancreasReleaseofpcel→GitracactiveincretinGLP-1GIPactivates(GLP-1GLP-1&GIPAdaptedfromDruckerDJ.CellMetab.2019:3:153-65RoleofIncretinSysteminGlu45GLP1和GIP是两类主要的肠促胰素0nzaGLP-1GIP(胰高糖素样肽-1)(葡萄糖依赖的促胰岛素释放多肽)主要合成部位L细胞K细胞(回肠和结肠)什十二指肠和空肠)2型糖尿病患者中分泌餐后胰高糖素↓食物摄入延缓胃排空促进β细胞增殖是是是是是是否否否否是是促进胰岛素生物合成DruckerD].DiabetesCare.2019:26:2929-2940.GLP1和GIP是两类主要的肠促胰素0nza46TheIncretinEffectisReducedinType2DiabeteshanzaResponsestoglucoseloadintype2diabeticsandhealthysubjectsaOralglucose(50g)Ivglucose(variable)Controlsubjects(N=8)Type2diabeticpatients(N=14)"Ps0.05totherespectivevalueaftertheoralloadTime(min)Time(min)00042Responsestoanoralglucoseloadof50gandintravenousglucoseinfusionweremeasuredin14type2diabeticpatientsand8healthycontrolAdaptedfromNauckM,etal.Diabetologia.1986;29:46-52TheIncretinEffectisReduced47IncretinhormonechangeshanzaGLP-1(pmol/L)Time(minutes)Inpatientswithtype2diabetes,levelsofGLP-1releasedinresponsetoglucosearereducedandglPactivityisdecreasedIncretinhormonechanges48ContinuousInfusionofGLP-1DecreasesFastingGlucoseaswellasHbA1chanzaComparedtosaline,patientstreatedwithGLP-1showedfastingand8-hourmeanplasmaglucosethatwasdecreasedby4.3mmouand5.5mmol/(P<00001),andHbA,cthatwasdecreasedby1.3%(P=0.003)Patientsassignedsaline(N=9PatientsassignedGLP-1(N=10)aWeekaWeek1三AdaptedfromZanderM,etal.Lancet.2019:359(9309):824-30.ContinuousInfusionofGLP-1D49ExogenousGlucose-DependentInsulinotropicPolypeptideWorsensPostprandialHyperglycaemiainType2DiabeteshanzaWhencomparedwithplacebo,exogenousGIPinfusionnotonlydidnotlowerpostprandialglucosebutfurtherworsenedhyperglycaemiaduringlatepostprandialperiod(120-360min)inpatientswithtype2diabetes(N=22)ChangesininsulinChangesinglucose