PKB/ Akt 在高脂诱导鼠肾脏损害中的作用

目的:通过建立高脂血症大鼠模型,探讨单纯高脂对肾脏的损伤机制以及胰岛素传导通路中的关键酶PKB/Akt(丝氨酸/苏氨酸激酶)在高脂所致肾脏损害中的变化和意义。方法:高脂高胆固醇喂养Wistar雄性大鼠,建立胰岛素抵抗模型。分别在4周、8周、12周测定大鼠的肾功,包括血尿素蛋(BUN),肌酐(CREA);16周时测定甘油三酯(TG),胆固醇(TC),以及血糖(FBS)和胰岛素(FINS)。8周时行胰岛素增敏剂文迪雅(3mg/kg)灌胃干预四周,并行肾脏病理检查,应用免疫组化法监测PKB/Akt在肾脏的表达。结果:高脂喂饲大鼠4周后,进食量开始减少,体重增加减慢;血BUN、血CREA在4周时已升高,至8周时增加更明显(p<0.001)。文迪雅灌胃四周后肾功改善,但仍高于正常组(p<0.05)。血TG和血TC较正常组升高显著,统计学差异显著(p<0.05)。血胰岛素升高,但胰岛素敏感性降低,胰岛素抵抗指数增加显著,提示胰岛素抵抗形成。肾脏免疫组化PKB/Akt的表达呈现为在肾小球和肾小管分布不均,出现PKB/Akt在损伤较重的肾小球不表达,而在损伤较轻的肾小管表达减弱的现象。结论:饮食诱导的高脂血症可导致健康大鼠产生脂质肾毒性损害以及肾功的降低,并可产生胰岛素抵抗。胰岛素传导通路的损害在肾小球和肾小管表达不同,说明其可能是产生肾脏损伤及胰岛素抵抗的又一原因。胰岛素增敏剂可改善胰岛素抵抗及肾功。     

高脂喂养大鼠肝脏的NF-κBp65表达与胰岛素抵抗的相关性

目的探讨高脂饲料喂养大鼠肝脏NF-κBp65蛋白的表达与胰岛素抵抗的关系。方法采用高脂饲料喂养建立胰岛素抵抗大鼠模型,并用正常血糖-高血浆胰岛素钳夹技术评估。应用Western blotting方法检测大鼠肝脏中NF-κBp65蛋白的表达。结果①高脂饲料组大鼠的葡萄糖输注率明显低于基础饲料组[GIR60~120（0.76±0.28vs4.26±0.70）mg/（kg.min）,P〈0.01]。②高脂饲料组大鼠肝脏NF-κBp65蛋白的表达明显高于基础饲料组（A值118.48±1.45vs68.13±4.84,P〈0.01）。③高脂胰岛素抵抗大鼠肝脏NF-κBp65蛋白表达与GIR60-120（r=-0.993,P=0.000）和ISI（r=-0.773,P=0.009）负相关。结论高脂诱导的胰岛素抵抗大鼠肝脏NF-κB的激活可能是产生肝脏和全身胰岛素抵抗的根源。     

高脂饮食和地塞米松联合诱导胰岛素抵抗大鼠模型

目的用高脂饲料＋地塞米松（dexamethasone,DEX）隔日腹腔注射建立实验性胰岛素抵抗大鼠模型,研究该模型糖代谢、脂代谢和激素水平等方面的变化。方法采用Wistar雄性大鼠,分为正常对照组、高脂组、DEX组（1mg/kg,i.p.）和高脂＋DEX组（1mg/kg,i.p.）,连续观察8周,每周测定大鼠空腹血糖,分别于造模第2周和第8周测糖耐量,8周后处死大鼠,测定胸腺、脾脏、肝脏等脏器重量。结果高脂饲料能加重腹腔注射DEX造成的空腹血糖升高,造模第8周空腹血糖（7.7±0.7）较空白组（6.5±0.6）显著升高。使模型动物糖耐量明显异常,肝糖原、肌糖原含量显著增加,血浆胰岛素及游离脂肪酸水平显著升高,各脏器指数明显增加。结论高脂＋DEX隔日腹腔注射能成功诱导胰岛素抵抗大鼠模型,这种造模方法较单纯注射DEX或单纯高脂饲养成模率高,造模周期短。     

干预脂毒性改善糖尿病大鼠胰岛素分泌及氧化应激的损害

目的探讨干预脂毒性改善糖尿病大鼠胰岛分泌功能及氧化应激损害的机制。方法将大鼠分为4组①正常组（NC）,全程普通饲料喂养;②高脂组（HF）,全程高脂饲料喂养。糖尿病组,高脂饲料喂养8周后腹腔注射低剂量STZ（30mg/kg）,48h后行OGTT试验判断成模情况后分组。③糖尿病对照组（DM）,不给予药物干预;④血脂干预组（SIM）,灌胃辛伐他汀5mg/（kg.d）4周干预脂毒性。通过免疫组化染色观察胰岛B、A细胞形态学特点,RT-PCR测定胰腺内胰岛素原mRNA表达水平,DHE荧光染色检测胰岛中活性氧化产物ROS水平。结果与糖尿病对照组相比,干预脂毒性4周后血清胆固醇（TC）和甘油三酯（TG）水平分别下降了22.9%（P〈0.01）和57.0%（P〈0.05）。OGTT血糖水平均显著下降（P〈0.01）。胰岛中B细胞相对量是对照组的2.6倍（P〈0.01）,B细胞胞质内胰岛素水平增加了26.5%（P〈0.05）,胰岛素原mRNA表达升高18.3%（P〈0.01）;A细胞相对量减少了50%（P〈0.01）。血清丙二醛（MDA）水平和胰腺中ROS表达显著下降。结论辛伐他汀干预脂毒性4周可以显著改善糖尿病大鼠胰岛分泌功能和氧化应激损害。     

运动对老年肥胖大鼠脂联素的影响

目的：探讨运动对老年肥胖大鼠内脏脂肪组织脂联素mRNA和蛋白质表达、血浆脂联素浓度及胰岛素抵抗的影响。方法：取雄性SD大鼠,鼠龄21 d,分青春期、壮年期和老年期三个阶段喂养高脂饲料（脂肪率为36.3%~40.0%）,建立老年肥胖模型。鼠龄达到60周后,取自然生长老年大鼠随机分为对照组（C）和老年运动组（AE）,n=6;取老年肥胖大鼠随机分为肥胖对照组（OC）和肥胖运动组（OE）,n=6。动物跑台坡度0°,运动速度及时间为（15 m/min×15 min）,4组/次,组间休息5 min,每次共运动60 min,5次/周,持续运动8周。8周后,检测内脏脂肪组织脂联素mRNA和蛋白质表达,测定血糖、血浆脂联素浓度和胰岛素浓度,计算胰岛素抵抗。结果：运动干预后,与对照组比较,肥胖对照组大鼠脂联素mRNA和蛋白质表达显著减低,血糖浓度和胰岛素抵抗明显增高;而老年运动组大鼠脂联素mRNA和蛋白质表达显著增高。与肥胖对照组大鼠比较,肥胖运动组大鼠脂联素mRNA和蛋白质表达显著增高、血浆脂联素水平增高,血糖浓度和胰岛素抵抗明显减低。结论：老年肥胖大鼠内脏脂肪组织脂联素mRNA和蛋白质表达均降低,伴随胰岛素抵抗、血糖升高。运动能显著增加其内脏脂肪组织脂联素mRNA和蛋白质表达,升高血浆脂联素水平,改善胰岛素抵抗,降低血糖。     

转化生长因子β1和snail1参与糖尿病大鼠肾小管上皮细胞向间充质细胞转变

本文旨在观察转化生长因子β1（transforming growth factor-β1,TGF-β1）和锌指转录因子Snail1在糖尿病（diabetes mellitus,DM）大鼠肾组织中的表达,并初步探讨它们与肾小管上皮细胞向间充质细胞转变的关系。链脲佐菌素（streptozotocin,STZ）诱发大鼠DM,按病程分为2、4、8、12、16、20、24周、16周胰岛素治疗（16wA）、20,周胰岛素治疗（20wA）和24周胰岛素治疗（24wA）组（n=6）。其中胰岛素治疗组动物从第13周起用胰岛素控制血糖至正常水平,每一时点均设鼠龄匹配的正常对照组。测定各组血糖、24h尿蛋白、血肌酐（serum creatinine,Scr）、肾脏指数。PAS染色光镜观察肾脏病理学改变。免疫组织化学检测肾脏Snail1、TGF-β1、α-平滑肌肌动蛋白（α-smooth muscle actin,α-SMA）、E-钙黏素和纤连蛋白（fibronectin,FN）的表达;Western blot检测肾皮质Snail1、TGF-β1和E-钙黏素蛋白表达。RT-PCR检测肾皮质Snail1和E-钙黏素mRNA表达。结果显示：（1）DM各组大鼠的血糖、24h尿蛋白、Scr、肾脏指数均较正常对照组明显升高（P〈0．05,P〈0．01）,胰岛素治疗组大鼠上述指标均较DM组显著降低（P〈0．01）。（2）TGF-β1和Snail1免疫组织化学阳性染色见于DM各组大鼠肾小管,正常对照组未见阳性表达,胰岛素治疗组大鼠弱阳性表达,并随治疗时间延长而减少。从16周开始在DM大鼠肾小管上皮细胞可见α-SMA蛋白阳性表达,胰岛素治疗组大鼠未见α-SMA蛋白表达;DM组大鼠E-钙黏素蛋白阳性染色明显少于正常对照组。（3）DM组大鼠肾皮质TGF-β1和Snail1蛋白以及Snail1 mRNA表达较正常对照组显著增高（P〈0．01）,胰岛素治疗组大鼠则显著低于DM组（P〈0．01）;DM组E-钙黏素mRNA和蛋白表达与TGF-β1和Snail1呈相反变化。结果提示,TGF-β1和Snail1可能参与DM大鼠肾小管上皮细胞向间充质细胞转变,胰岛素治疗可抑制两者表达并阻断肾小管上皮细胞向间充质细胞转变。     

运动干预对胰岛素抵抗大鼠骨骼肌IL-1β表达的影响

目的观察运动干预对高脂饲料诱导胰岛素抵抗（IR）大鼠白细胞介素1β（IL-1β）表达的影响,探讨运动减轻IR的可能机制。方法健康Wistar雄性大鼠分为基础饲料喂养组（normal chow group,NC）,高脂膳食喂养组（high-fat diet group,HF）。高脂膳食喂养Wistar雄性大鼠10周,构建IR动物模型。10周后,HF组再随机分为高脂喂养运动组和非运动组,游泳运动干预4周。游泳运动干预前后以正常血糖-高血浆胰岛素钳夹实验技术[hyperinsulinemic-euglycemic clamp（HEC）technique]评估IR大鼠胰岛素敏感性,ELISA法测定大鼠血清IL-1β水平,RT-PCR法测定大鼠骨骼肌IL-1βmRNA表达。结果HF组大鼠葡萄糖输注率（glucose infusion rate,GIR）显著低于NC组（P〈0.05）,HF组血清IL-1β水平及骨骼肌组织IL-1βmRNA表达明显高于NC组（P〈0.05,P〈0.01）;运动组大鼠血清IL-1β水平及骨骼肌组织IL-1βmRNA表达明显低于非运动组（P〈0.05）,与NC组差异无显著性（P〉0.05）。结论运动改善IR大鼠胰岛素敏感性,可能与降低IR大鼠IL-1β的表达有关。     

运动对肥胖大鼠胰岛素抵抗的影响

目的：探讨急、慢性游泳运动对胰岛素抵抗大鼠半乳凝素-3（galectin-3）表达的影响。方法：100只大鼠随机分为：普通膳食对照组（CON组,n=10）;高脂膳食组（HFD组,n=90）。分别喂养8周后,从高脂膳食组筛选出肥胖（即体重位于上游）大鼠30只用于后续实验。将肥胖大鼠随机分为3组（n=10）：①HFD-SED组：高脂膳食安静组;②HFD-CE组：高脂膳食慢性运动组,进行慢性游泳运动;③HFD-AE组：高脂膳食急性运动组,进行急性游泳运动。肥胖大鼠继续高脂膳食喂养8周,并进行运动干预;CON组大鼠继续普通饲料喂养8周。运动干预结束后,各组进行口服糖耐量和胰岛素释放实验,计算葡萄糖-胰岛素指数;测定体重;以ELISA分析大鼠血液中Gal-3含量。结果：HFD-SED组葡萄糖-胰岛素指数明显大于CON组（P<0.01）,HFD-CE组和HFD-AE组葡萄糖-胰岛素指数明显小于HFD-SED组（P<0.01）;HFD-SED组血液Gal-3含量明显高于CON组（P<0.01）,HFD-CE和HFD-AE组血液Gal-3含量明显小于HFD-SED组（P<0.01）。运动干预结束后,HFD-SED组和HFD-AE组大鼠体重明显高于CON组（P<0.01）;HFD-CE组大鼠体重明显低于HFD-SED组（P<0.01）,而与CON组无统计学差异。结论：急、慢性游泳运动均能改善胰岛素抵抗状态、降低胰岛素抵抗大鼠的Gal-3表达,但慢性游泳运动能明显改善机体超重状态。建议临床上采用长期、规律的慢性有氧运动对肥胖、胰岛素抵抗等代谢疾病进行干预。     

胰岛素抵抗大鼠的肝脏中丝氨酸/酪氨酸磷酸化异常与血清TNF-α相关

目的探讨胰岛素抵抗大鼠胰岛素受体底物-1丝氨酸/酪氨酸磷酸化与肿瘤坏死因子α（TNF-α）的关系。方法雄性Wistar大鼠30只（体质量80-120 g）,随机分为普通饮食组（NC）及高脂饮食组（FH）2组,每组15只。喂养10周,以高胰岛素-正常血糖钳夹技术评估胰岛素抵抗大鼠模型。应用ELISA法检测大鼠血清TNF-α含量,Western Blot法检测肝脏组织中胰岛素受体底物-1丝氨酸磷酸化（IRS-1Ser636）及酪氨酸磷酸化（IRS-1Tyr465）表达。结果FH组葡萄糖输注率（GIR）60-120水平明显低于NC组[（1.56±0.43 vs.5.15±0.66）mg/（kg.min）,P〈0.01];FH组大鼠TNF-αI、RS-1Ser636均高于NC组[（15.43±2.16 vs.5.4±2.16）pg/mL,P〈0.01;（109.45±13.75 vs.94.23±15.05）,P〈0.05],IRS-1Tyr456水平低于NC组[（111.08±14.28 vs.125.77±14.51）,P〈0.05]。TNF-α水平与IRS-1Ser636呈正相关（r=0.503,P=0.024）,与IRS-1Tyr465呈负相关（r=-0.521,P=0.019）。结论胰岛素抵抗大鼠TNF-α水平与IRS-1Tyr465负相关,与IRS-1Ser636正相关,提示TNF-α引起胰岛素抵抗机制可能与IRS-1磷酸化异常有关。     

不同脂肪高脂日粮诱发胰岛素抵抗综合征大鼠模型的比较

目的分析猪油、豆油、氢化椰子油、乳脂四种不同脂肪的高脂日粮分别诱发胰岛素抵抗综合征（IRS）大鼠的血液生化指标差异,为此类模型的建立及实验研究提供参考。方法雄性SD大鼠随机分为5组,对照组给予普通日粮,高脂组给予脂肪热量比相同的高脂日粮。喂养6周,每两周测定空腹血糖、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-c）、总胆固醇（TC）、胰岛素,根据胰岛素敏感性指数（ISI）=ln1/（FPG×FINS）评定大鼠的胰岛素敏感性。结果6周后,猪油组、乳脂组、豆油组血清胰岛素均显著高于对照组（P〈0.05）;乳脂组血清TG显著高于其它高脂组（P〈0.05）;高脂组血清HDL-c均显著低于对照组（P〈0.05）并以豆油组下降幅度最大;猪油组、乳脂组ISI显著低于对照组（P〈0.05）;而各组间血清总胆固醇、血糖及体重无明显差异（P〉0.05）。结论4种高脂日粮诱发IRS大鼠模型的综合效果依次为乳脂、猪油、豆油、氢化椰子油。     

TyrB26位点改变的人类胰岛素类似物的化学合成与体外活性

摘要：为了研究人类胰岛素B链第26位的酪氨酸对胰岛素和受体之间的结合的影响,包括单独的氨基酸替换或化合物替换的不同的胰岛素类似物被合成,其中化合物替代的类似物的B链C末端都减少了4个氨基酸。在对它们与胰岛素受体的亲和力进行研究中,结果发现它们与胰岛素受体的亲和力没有丢失, HisB26类似物和N-MeHisB26类似物的结合能力与胰岛素相比改变不大,分别是胰岛素的72 %和107 %。N-MeGluB26类似物,AadB26类似物和Phe (4-carboxy) B26类似物的结合能力有很大的提高,分别是130 %, 234 %和160 %。     

胰岛素对βTC-3细胞胰岛素受体表达的作用

目的：观察外源性胰岛素对小鼠胰岛β细胞瘤细胞株βTC-3细胞胰岛素受体表达的影响。方法：采用免疫荧光细胞化学技术结合激光扫描共聚焦显微镜观察高浓度胰岛素（100 IU/ml）刺激不同时间（0 min、30 min、60 min、120 min、240 min）,培养的βTC-3细胞胰岛素受体的表达,用Image pro plus软件对胰岛素受体的荧光强度进行了半定量分析。结果：与0 min比较,胰岛素孵育30 min、60 min、120 min、240 min时胰岛素受体荧光强度均明显下降（P〈0.05）。结论：高浓度胰岛素孵育βTC3细胞后,可明显下调胰岛素受体的表达,这可能是高胰岛素血症导致胰岛素抵抗产生的机制之一。     

Dual microcolumn immunoassay applied to determination of insulin secretion from single islets of Langerhans and insulin in serum

A dual microcolumn immunoassay (DMIA) was developed and applied to determination of insulin in biological samples. The DMIA utilized a protein G capillary column (150 μm I.D.) with covalently attached anti-insulin to selectively capture and concentrate insulins in a sample. Insulins retained in the capillary immunoaffinity column were desorbed and injected onto a reversed-phase capillary column (150 μm I.D.) for further separation from interferences such as cross-reactive antigens and non-specifically adsorbed sample components. Bovine, porcine and rat insulin all cross-reacted with the antibody and could be determined simultaneously. Using a UV absorbance detector, the dual microcolumn system had a detection limit of 10 fmol or 20 pM for 500-μl sample volumes. The DMIA system was used to measure glucose-stimulated insulin secretion from single rat islets of Langerhans. Because of the separation in the second dimension, both rat I and rat II insulin could be independently determined. The system was also evaluated for determination of insulin in serum. Using microcolumns instead of conventional HPLC columns resulted in several advantages including use of less chromatographic material and improved mass detection limit.     

Labeling of insulin with non-radioactive I and application to incorporation of radioactive I for use in receptor-binding experiments by high-performance liquid chromatography

Conditions for the labeling of insulin with radioactive iodine isotopes were investigated by means of incorporation of non-radioactive ¹²⁷I into the peptide. Either the chloramine-T (CT) or lactoperoxidase-hydrogen peroxide (LPO) technique was applied and reversed-phase high-performance liquid chromatography (RP-HPLC) was used for analysis of the reaction products. The LPO method provided the ¹²⁷I-labeled peptide within 15–30 min, whereas the CT alternative yielded the labeled substrate even within 15 s. However, the latter reaction can only be controlled in a reproducible manner with difficulty and undesirad side-reactions became increasingly prominent when t a few seconds. In another experiment, the LPO technique was applied for radiolabeling insulin with ¹²⁵I. The product was first purified by size-exclusion chromatography (SEC) and then subjected to RP-HPLC. SEC yielded two peaks. The smaller one, which eluted at a slightly higher K_d value (accounting for about 14% of total radioactivity) predominantly consisted of material eluting at the column's void volume under the conditions of RP-HPLC, whereas the main SEC fraction (accounting for about 86% of total radioactivity) yielded a single peak, as shown by HPLC. The radioactive material attributable to the main SEC fraction revealed the expected receptor-binding properties, as evidenced by displacement experiments with non-radioactive insulin, as well as the action of tetradecanoyl phorbol acetate on the binding characteristics and thus indicating formation of a labeled hormone retaining biological activity.     

胰岛素信号转导障碍与胰岛素抵抗的形成

胰岛素生理作用的发挥,起始于胰岛素与其受体的结合,并由此引起细胞内一系列信号转导,最终到达各效应器产生各种生理效应。胰岛素信号转导在胰岛素生理作用的发挥中起着至关重要的作用。胰岛素信号转导减弱或受阻,使得胰岛素生理作用减弱,导致胰岛素抵抗形成。本文综述了胰岛素信号转导失调在胰岛素抵抗形成中的作用。     

Blockade of IRS1 in isolated rat pancreatic islets improves glucose-induced insulin secretion

Several neural, hormonal and biochemical inputs actively participate in the balance of insulin secretion induced by blood glucose fluctuations. The exact role of insulin as an autocrine and paracrine participant in the control of its own secretion remains to be determined, mostly due to insufficient knowledge about the molecular phenomena that govern insulin signaling in pancreatic islets. In the present experiments we demonstrate that higher insulin receptor and insulin receptor substrates-1 and -2 (IRS1 and IRS2) concentrations are predominantly encountered in cells of the periphery of rat pancreatic islets, as compared to centrally located cells, and that partial blockade of IRS1 protein expression by antisense oligonucleotide treatment leads to improved insulin secretion induced by glucose overload, which is accompanied by lower steady-state glucagon secretion and blunted glucose-induced glucagon fall. These data reinforce the inhibitory role of insulin upon its own secretion in isolated, undisrupted pancreatic islets.     

Insulin receptor-inspired soluble insulin binder

The insulin receptor (IR) is a 320 kDa membrane receptor tyrosine kinase mediating the pleiotropic actions of insulin, leading to phosphorylation of several intracellular substrates including serine/threonine-protein kinase (AKT1), and IR autophosphorylation. Structural details of the IR have been recently revealed. A high-binding insulin site, L1 (K_d =2 nM), consists of two distant domains in the primary sequence of the IR. Our design simplified the L1 binding site and transformed it into a soluble insulin binder (sIB). The sIB, a 17 kDa protein, binds insulin with 38 nM affinity. The sIB competes with IR for insulin and reduces by more than 50% phosphorylation of AKT1 in HEK 293 T cells, with similar effects on IR autophosphorylation. The sIB represents a new tool for research of insulin binding and signaling properties.     

Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII

Insulin regulates blood glucose by promoting uptake by fat and muscle, and inhibiting production by liver. Insulin-stimulated glucose uptake is mediated by GLUT4, which translocates from an intracellular compartment to the plasma membrane. GLUT4 traffic and insulin secretion both rely on calcium-dependent, regulated exocytosis. Deletion of the voltage-gated potassium channel Kv1.3 results in constitutive expression of GLUT4 at the plasma membrane. Inhibition of channel activity stimulated GLUT4 translocation through a calcium dependent mechanism. The synaptotagmins (Syt) are calcium sensors for vesicular traffic, and Syt VII mediates lysosomal and secretory granule exocytosis. We asked if Syt VII regulates insulin secretion by pancreatic beta cells, and GLUT4 translocation in insulin-sensitive tissues mouse model. Syt VII deletion (Syt VII -/-) results in glucose intolerance and a marked decrease in glucose-stimulated insulin secretion in vivo. Pancreatic islet cells isolated from Syt VII -/- cells secreted significantly less insulin than islets of littermate controls. Syt VII deletion disrupted GLUT4 traffic as evidenced by constitutive expression of GLUT4 present at the plasma membrane of fat and skeletal muscle cells and unresponsiveness to insulin. These data document a key role for Syt VII in peripheral glucose homeostasis through its action on both insulin secretion and GLUT4 traffic.     

The insulin receptor substrate-1: a biomarker for cancer?

This review focuses on IRS-1 and the evidence of its role in cell transformation. The literature strongly suggests that IRS-1 should be considered a biomaker for cancers susceptible to IGF-IR targeting. In addition, I would like to propose that IRS-1 may have a more general role in cancer, and could be considered as a protein having the opposite effect of tumor suppressors, a sort of anti-p53 molecule.     

门冬胰岛素、地特胰岛素、甘精胰岛素分别联合二甲双胍对糖尿病孕妇妊娠结局的影响

摘要 目的：探究门冬胰岛素、地特胰岛素、甘精胰岛素分别联合二甲双胍对糖尿病孕妇妊娠结局的影响。方法：随机抽取本院400例妊娠期糖尿病产妇为研究对象，按照简单随机法分为对照组（n=100例）、试验A组（n=100例）、试验B组（n=100例）和试验C组（n=100例）。对照组采用口服二甲双胍治疗，试验A、B、C组，分别采用门冬胰岛素、地特胰岛素、甘精胰岛素联合二甲双胍治疗。对比四组产妇的分娩方式，各产程时间，体重指数（BMI）、随机血糖、内脂素、脂联素的水平，妊娠并发症发生率，新生儿结局。结果：试验A、B、C组的自然分娩率均高于对照组（P<0.05），且试验A组的自然分娩率均高于试验B组、试验C组（P<0.05），试验B组、试验C组的自然分娩率对比无差异（P>0.05）；对照组、试验A、B、C组自然分娩产妇的第一产程、第二产程、第三产程时间对比无差异（P>0.05）；试验A、B、C组的BMI指数、随机血糖、内脂素、脂联素的水平均低于对照组（P<0.05），且试验A组的BMI指数、随机血糖、内脂素、脂联素的水平均低于试验B组、试验C组（P<0.05），试验B组、试验C组的BMI指数、随机血糖、内脂素、脂联素的水平对比无差异（P>0.05）；试验A、B、C组的妊娠并发症发生率均低于对照组（P<0.05），且试验A组的妊娠并发症发生率低于试验B组、试验C组（P<0.05），试验B组、试验C组的妊娠并发症发生率对比无差异（P>0.05）；试验A、B、C组的新生儿不良结局发生率均低于对照组（P<0.05），且试验A组的新生儿不良结局发生率低于试验B组、试验C组（P<0.05），试验B组、试验C组的新生儿不良结局发生率对比无差异（P>0.05）。结论：门冬胰岛素、地特胰岛素、甘精胰岛素分别联合二甲双胍均能够提高糖尿病孕妇妊娠的自然分娩率，降低BMI指数、随机血糖、内脂素、脂联素的水平，降低妊娠并发症发生率，改良新生儿不良结局，其中门冬胰岛素的疗效最好，具有较强的临床推广价值。