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1、第三十二章胰岛素及口服降糖药糖尿病(diabetesmellitus,DM):胰岛素分泌绝对或相对不足,引起糖、脂肪、蛋白质代谢紊乱的疾病。糖尿病诊断标准被确定为任何时候血糖≥11.1毫摩尔/升(≥200毫克/分升),和(或)空腹血糖≥7.0毫摩尔/升(≥126毫克/分升),则可以诊断为糖尿病胰腺pancreas糖尿病分类Ⅰ型(insulin-dependentdiabetesmellitus,IDDM)自身免疫性疾病–细胞破坏,胰岛素分泌缺乏Ⅱ型(non-insulin-dependentdiabetesmellitus,NIDDM)细胞功
2、能低下,胰岛素相对缺乏、胰岛素抵抗(INR)TypeIorinsulin-dependentdiabetesmellitusistheresultofafrankdeficiencyofinsulin.Theonsetofthisdiseasetypicallyisinchildhood.ItisduetodestructionpancreaticBcells,mostlikelytheresultofautoimmunitytooneormorecomponentsofthosecells.Manyoftheacuteeffectsofthisd
3、iseasecanbecontrolledbyinsulinreplacementtherapy.Maintainingtightcontrolofbloodglucoseconcentrationsbymonitoring,treatmentwithinsulinanddietarymanagementwillminimizethelong-termadverseeffectsofthisdisorderonbloodvessels,nervesandotherorgansystems,allowingahealthylife.TypeIIorn
4、on-insulin-dependentdiabetesmellitusbeginsasasyndromeofinsulinresistance.Thatis,targettissuesfailtorespondappropriatelytoinsulin.Typically,theonsetofthisdiseaseisinadulthood.Despitemonumentalresearchefforts,thenatureofthedefecthasbeendifficulttoascertain-insomepatients,theinsu
5、linreceptorisabnormal,inothers,oneormoreaspectsofinsulinsignallingisdefective,andinothers,nodefecthasbeenidentified.Becausethereisnot,atleastinitially,aninabilitytosecreteadequateamountsofinsulin,insulininjectionsarenotusefulfortherapy.Ratherthediseaseiscontrolledthroughdietar
6、ytherapyandhypoglycemicagents.糖尿病治疗方法及展望Ⅰ型糖尿病普通胰岛素替代疗法(猪、牛胰岛素注射)普通胰岛素结构改造(猪胰岛素链第30位的丙氨酸用苏氨酸代替)重组DNA技术利用大肠杆菌合成胰岛素Ⅱ型糖尿病控制饮食药物治疗常用药物种类磺酰脲类双胍类-葡萄糖苷酶抑制剂胰岛素增敏剂(罗格列酮、吡格列酮)餐时血糖调节剂(瑞格列奈)胰岛素治疗第一节胰岛素胰岛素的结构分子量为58kD的酸性蛋白质由两条多肽链以二硫键共价相连A链有21个氨基酸残基B链有30个氨基酸残基。(1)糖代谢:增加全身组织(脑除外)对葡萄糖的摄取和利用,减
7、少血糖的来源。1.加速心肌、骨骼肌和脂肪细胞膜上载体(Glut-4)转运葡萄糖进入细胞内。2.促进肝脏等器官对葡萄糖的氧化和酵解。3.促进肝、肌肉的器官的糖原的合成。4.促进葡萄糖转化为脂肪和氨基酸。5.抑制糖异生:抑制糖异生的关键酶[作用]Insulin-mediatedglucoseuptake-Insulinbindingtotheinsulinreceptorinducesasignaltransductioncascadewhichallowstheglucosetransporter(GLUT4)totransportglucosein
8、tothecell.糖酵解糖异生丙酮酸羧化酶磷酸烯醇式丙酮酸羧激酶1,6-二磷酸果糖磷酸酶葡萄糖-6-磷酸酶丙酮酸激酶6-