病例Case1:A11yearoldgirlisbroughttohospital.Shehaslostalmost4kgoverthepastmonthandahalfdespitebeinghungryandovereating.Shealsowasexcessivelythirstyandhasavoluminousurineoutput(polyuria).Physicalexamination:Sheisathinlittlegirl.BP:85/50;pulse:105.Laboratorytests:bloodglucose:40mmol/L(Normal:3.9-6.1mmol/L).Urine:5%glucose.Shehadlittle-cellfunctioninpancreas.Diagnosis:IDDM.Astreatment,insulinwasadministeredtothegirl.Withinsulininjections,thepatienthasbeenapparentlycontrolled.Case2:A53-year-oldmanhadbeeningoodhealthuntilabouttwomonthsagowhenhestartedtofeelweakandtiredmorerapidlythanusual.Onquestioning,headmittedtogettinguptwoorthreetimesanighttourinate.Healsoisoftenthirstyatthosetimesanddrinksaglassofwatereachtime.Hehadgraduallygainedweightovertheyears.Hisappetiteremainedexcellentbuthenowwaslosingweightandbecomingweak.Thepaininhisfeetwasworseatnightandsometimeskepthimawake.Itwasburningincharacterandsometimeshistoesfeltnumb.Hisvisionwasblurryattimes,especiallyintheafternoon.Physicalexamination:obese,pulse76,regular,BP142/78.Feet:skindrywithcallusesonthemedialsideofthebigtoes,Nailsnormal.Laboratorytests:randombloodglucose:25.3mmol/l,glycohemoglobin(HbA1c)16.4%,urinalysis:4+glucose.Diagnosis:NIDDM.ThedoctorprescribedAmaryl(glimepiride,stimulatetheisletcellsinthepancreastoproducemoreinsulin),4mg.aday.Otherclassesoforaldiabetesagentsare:Biguanides(decreasesthereleaseofglucosebytheliver,andmakesothercellsmoresensitivetoinsulin),Thiazolidinediones(TZDs)(increasescellularsensitivitytoinsulinanddecreasesthereleaseofglucosebytheliver).Dysfunctionofcellularsignaltransductionindisease细胞信号传导异常与疾病华中科技大学同济医学院病理生理系细胞信号转导指细胞通过胞膜或胞内受体感受信息分子的刺激，经细胞内信号转导系统转换,从而影响细胞生物学功能的过程细胞信号转导紧密连接细胞:间隙连接:电兴奋传递膜结合信号分子:粘附分子有距离的细胞:内分泌旁分泌自分泌突触信号传递(50nm)细胞信号物理刺激信号化学信号(配体)体液因子,气体分子,药物,细胞代谢物其它:细胞粘附分子Generalprocessfortransmembranesignaltransduction细胞信号转导的主要途径G蛋白介导的细胞信号转导途径Ga腺苷酸环化酶途径Gi抑制腺苷酸环化酶活性GqIP3、Ca2+-钙调蛋白激酶途径DG-蛋白激酶C途径其他:非G蛋白介导的细胞信号转导途径受体酪氨酸蛋白激酶途径非受体酪氨酸蛋白激酶途径鸟苷酸环化酶信号转导途径核受体及其信号转导途径ReceptorTyrosineKinases•细胞信号传导异常与疾病一、细胞外信号分子异常:过多谷氨酸↑门冬氨酸↑NMDAR钙内流激活钙依赖的酶兴奋性神经毒癜痫神经退行性疾病细胞外信号分子异常:缺乏胰岛细胞受损胰岛素↓高血糖糖尿病(Ⅰ型)受体病(receptordisease):因受体的数量、结构或调节功能变化，使受体不能正常介导配体在靶细胞中应有的效应所引起的疾病。二、受体异常与疾病受体的调节受体数量的调节向上调节(downregulation):受体数量增加受体增敏(hypersensitivity):在缺乏配体时自发激活或对正常配体反应性增强向下调节(upregulation):受体数量减少受体减敏(desensitization):细胞对配体刺激的反应性减弱2.亲和力的调节磷酸化受体的寡聚化受体的变构分类累及的受体主要临床特征遗传性受体病膜受体异常家族性高胆固醇血症LDL受体血浆LDL升高，动脉粥样硬化家族性肾性尿崩症ADHV2型受体男性发病，多尿、口渴和多饮c视网膜色素变性视紫质进行性视力减退cccccccccccccccc遗传性色盲视锥细胞视蛋白色觉异常11111111111111严重联合免疫缺陷症IL-2受体γ链T细胞减少或缺失，反复感染ccccccccccccccccII型糖尿病胰岛素受体高血糖,血浆胰岛素正常或升高ccc核受体异常ccc雄激素抵抗综合征雄激素受体不育症，睾丸女性化cccccccccccc...
