胰岛素抵抗肝细胞多药耐药基因1的表达

目的体外观察诱导发生胰岛素抵抗（IR）肝细胞中多药耐药基因1（mdr1）的表达。方法采用高浓度胰岛素诱导肝源性细胞HepG2建立IR细胞模型（HepG2/IR细胞）,GOD-POD微量化法测定葡萄糖消耗量,RT-PCR检测HepG2/IR细胞mdr1和胰岛素受体（InsR）基因mRNA的表达,流式细胞术检测P糖蛋白（P-gp）和InsR蛋白水平。结果HepG2/IR细胞葡萄糖消耗量降低10%～45%,InsR基因mRNA表达显著下调,受体表达量降低50.2%～82.9%;mdr1表达显著增强,mRNA转录增高0.7～2.1倍,P-gp表达阳性细胞增加0.6～1.7倍,表达强度增高。结论IR肝细胞mdr1和P-gp的表达显著增强。     

吡格列酮对胰岛素抵抗HepG2细胞胰岛素受体底物表达的影响

目的探讨毗格列酮对胰岛索抵抗（IR）HepG2细胞胰岛素受体底物（IRS）蛋白表达的影响。方法胰岛素抵抗HepG2细胞模型建立后,培养液中加入吡格列酮共同孵育,观察吡格列酮对模型细胞葡萄糖掺入率的影响;应用免疫细胞化学染色法观察吡格列酮对IR HepG2细胞IRS-1、IRS-2表达的影响。结果与模型细胞组比较,1×10^-5mol／L吡格列酮显著提高了HepG2细胞的葡萄糖掺入率（P〈0．01）,使IRHepG2细胞IRS-1、IRS-2蛋白的表达显著增加（P〈0．05）。结论吡格列酮的胰岛素增敏作用可能与胰岛素信号转导分子IRS-1、IRS-2蛋白的表达增强有关。     

蜕皮甾酮对2型糖尿病大鼠肝细胞IR S-2蛋白表达的影响

目的：探讨蜕皮甾酮对2型糖尿病大鼠肝细胞胰岛素受体底物2（ IRS-2）蛋白表达的影响。方法选择42只大鼠,14只作为正常组,常规饲料喂养,余下28只先以高脂喂养加小剂量STZ注射诱导2型糖尿病大鼠模型,造模成功后,随机分为模型组和治疗组,分别给予高脂饲料喂养、高脂饲料喂养＋蜕皮甾酮灌胃治疗。5周后取大鼠肝组织标本,应用免疫组化和RT-PCR技术检测IRS-2蛋白和mRNA含量。结果正常组和治疗组肝细胞IRS-2蛋白及mRNA含量均明显高于模型组（ P＜0．05或＜0．01）。结论蜕皮甾酮可提高2型糖尿病大鼠肝细胞IRS-2蛋白和mRNA含量,这可能是蜕皮甾酮改善2型糖尿病大鼠胰岛素抵抗的机制之一。     

胰岛素抵抗肝癌细胞IGF-1R/NF-κB表达及多药耐药机制研究

目的 探讨胰岛素抵抗（IR）肝癌细胞胰岛素样生长因子1受体（IGF-1R）和核因子-κB（NF-κB）表达变化及多药耐药（MDR）发生机制。方法 采用高浓度胰岛素诱导人肝癌细胞（HepG2和HepG2.2.15）建立胰岛素抵抗（IR）细胞模型。采用Western blot 法检测胰岛素受体（InsR）、IGF-1R、NF-κB 和 P-糖蛋白（P-gp）表达变化。使用流式细胞仪（Annexin V-FITC法）检测阿霉素对细胞凋亡的影响。结果 分别用100 nmol/L 和 1 000 nmol/L 胰岛素培养 HepG2 和 HepG2.2.15 细胞 48 h,成功建立 IR 肝癌细胞模型;IR 肝癌细胞 IGF-1R、NF-κB、P-gp 表达上调,而InsR 表达下调;应用 25μg/mL 阿霉素作用细胞 24 h 后,IR-HepG2 细胞组凋亡率（31.1%±1.9%）显著低于HepG2 细胞组【（49.7%±2.2%）,P＜0.01】,IR-HepG2.2.15细胞凋亡率【（20.1±1.7） %】显著低于 HepG2.2.15 细胞【（33.8±1.8）%,P＜0.01】;HepG2.2.15 和 IR-HepG2.2.15 细胞凋亡率分别较 HepG2 和 IR-HepG2 细胞显著降低（P＜0.01）。结论 IGF-1R/NF-κB/P-gp 过表达可能介导 IR 肝癌细胞对阿霉素的多药耐药。     

复方石斛合剂调节胰岛素受体表达促进HepG2细胞糖代谢

目的 探讨复方石斛合剂增加HepG2细胞胰岛素信号促进葡萄糖代谢的机制.方法 以高胰岛素培养HepG2细胞24 h,诱导胰岛素抵抗(IR)状态,继以10％复方石斛合剂的含药血清干预48 h,测定细胞6-磷酸果糖激酶、异柠檬酸脱氢酶的活性,RT-PCR与免疫印迹胰检测岛素受体mRNA与蛋白水平的表达.结果 高浓度胰岛素能降低6-磷酸果糖激酶、异柠檬酸脱氢酶的活性,降低胰岛素受体的表达;复方石斛合剂的治疗能增加6-磷酸果糖激酶、异柠檬酸脱氢酶的活性(P＜0.05),促进胰岛素受体的转录与翻译水平表达(P＜0.05),逆转高胰岛素的下调影响.结论 高浓度胰岛素可诱发IR,复方石斛合剂能增加HepG2细胞胰岛素受体的表达,提高葡萄糖分解代谢关键酶活性,缓解IR.     

阿尔茨海默病海马细胞胰岛素受体和胰岛素样生长因子Ⅰ受体的异常表达

目的 探讨阿尔茨海默病(AD)和2型糖尿病(T2DM)的病理联系,从受体水平探讨AD是否存在和T2DM类似的抵抗机制.方法 用梯度浓度的淀粉样蛋白(Aβ1-42)处理体外培养的海马神经细胞,制作AD细胞模型,用流式细胞法检验成模,使用RT-PCR法和Western印迹法检测胰岛素受体(InsR)和胰岛素样生长因子Ⅰ受体(IGF-ⅠR)基因水平和蛋白水平的表达,对比AD细胞和正常细胞受体表达的变化.结果 经流式细胞术筛选,当Aβ1-42浓度≥30 μmol/L时,细胞较对照组出现明显凋亡,可以模拟AD病理状态.在各浓度梯度组,Aβ1-42 30和60 μmol/L组的InsR和IGF-ⅠR表达在基因和蛋白水平均较对照组升高(P＜0.01);在Aβ1-42 100 μmol/L组,两者均较对照组下降(P＜0.05).两受体变化趋向一致.结论 AD脑中可能存在着对胰岛素和胰岛素样生长因子Ⅰ的抵抗,与T2DM共享相同的发病机制.     

慢性胰岛素刺激对胰岛素受体后不同信号转导途径的下降调节

目的　研究胰岛素慢性刺激对人肝癌细胞株 (HepG2 )胰岛素受体后不同信号转导途径的影响。方法　HepG2 细胞在无血清条件下与不同浓度的胰岛素 ( 0～ 10 0nmol/L)温育 16h ,然后用 10 0nmol/L胰岛素急性刺激 1min。这些细胞的溶解物中的胰岛素受体 β亚单位 (IRβ) ,胰岛素受体底物 (IRS) 1,IRS 2 ,磷酯酰肌醇 3激酶 (PI3K)的调节亚单位P85 ,有丝分裂原激活蛋白激酶 (MAPK)的蛋白表达水平和MAPK的磷酸化水平通过Western免疫印迹法测定 ,IRβ、IRS 1/ 2的蛋白磷酸化水平以及IRS 1/ 2与P85的结合反应用特异性抗体的免疫沉淀法。结果　胰岛素 1min急性刺激能迅速导致IRβ、IRS 1、IRS 2的酪氨酸磷酸化和MAPK的磷酸化 ,以及IRS 1( 2 )与P85的相互作用而激活PI3K。高浓度胰岛素慢性刺激显著降低了IRβ、IRS 1和IRS 2的酪氨酸磷酸化。细胞用 10 0nmol/L胰岛素预温育 16h后 ,IRβ、IRS 1和IRS 2的磷酸化水平降至最低值 ,分别为对照水平的 2 2 .2 % (P <0 .0 1)、10 .9% (P <0 .0 1)和 2 2 .0 % (P<0 .0 1) ,与IRS的磷酸化变化相平行 ,IRS 1和IRS 2与PI3K的相互作用分别降低至对照水平的 3 4.3 %(P <0 .0 1)和 3 0 .0 % (P <0 .0 1) ,MAPK的磷酸化水平降低至对照水平的 16.4% (P <0 .0 1)。IRβ的蛋白表达水平     

苦酸通调方对HepG2细胞胰岛素抵抗模型中IRS-1、PI3K、Akt蛋白表达的影响

目的观察苦酸通调方对HepG2细胞胰岛素抵抗(IR)模型中内胰岛素受体底物(IRS)-1、磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)信号分子的影响并探讨相关机制。方法通过0.25 mmol/L棕榈酸联合30 mmol/L高糖孵育24 h诱导HepG2 IR细胞模型,予以不同浓度的苦酸通调方(50,100,200μg/ml)。葡萄糖试剂盒检测细胞培养液上清葡萄糖含量,肝糖原试剂盒测定HepG2细胞内肝糖原含量,蛋白免疫印迹法(Western印迹)检测细胞内IRS-1、PI3K、Akt的蛋白表达。结果与模型组相比,苦酸通调方干预后,呈剂量依赖性增加IR HepG2细胞的葡萄糖消耗量及细胞内肝糖原含量(P<0.05),上调IRS-1、PI3K、Akt蛋白磷酸活化水平(P<0.05)。结论苦酸通调方改善2型糖尿病IR作用可能与影响IRS-1、PI3K、Akt蛋白表达相关。     

n-3多不饱和脂肪酸对高脂诱导胰岛素抵抗大鼠肝脏和骨骼肌胰岛素受体及葡萄糖转运蛋白4的作用

目的探讨n-3脂肪酸对饱和脂肪酸诱导的大鼠胰岛素抵抗(IR)肝脏和骨骼肌胰岛素受体(InsR)及葡萄糖转运蛋白4(GluT-4)的作用。方法45只雄性Wistar大鼠分为对照组、高脂组和n-3脂肪酸组。各组饲养11周后测定有关指标。结果(1)与对照组比较，高脂组大鼠体内脂肪相对含量、空腹血糖(FBG)、血清胰岛素(Ins)、甘油三酯(TG)、胆固醇(TC)、胰岛素抵抗指数(IRI)、肝脏TC和TG含量、肌肉中TG含量均显著升高；而肌肉组织中TC含量无显著改变，高脂组肝脏和肌肉InsR含量、肌肉Glut-4蛋白的相对含量均明显下降。(2)n-3脂肪酸组体内脂肪相对含量、FBG、Ins、TG、TC、IRI、肝脏TC和TG含量、肌肉组织中TG含量较高脂组均明显降低，肝脏InsR含量和肌肉GluT-4较高脂组明显升高。结论适量n-3脂肪酸代替饱和脂肪酸的一部分热量后，可增加IR大鼠肝脏InsR含量和肌肉GluT-4蛋白表达。     

软脂酸诱导HepG2细胞胰岛素抵抗及花生四烯酸防治作用的机制研究

目的 探讨高浓度软脂酸(PA)诱导HepG2细胞胰岛素抵抗(IR)的机制及花生四烯酸(AA)对IR的防治作用。方法 (1)用高浓度软脂酸(PA)或10^-7mol／L高胰岛素(HI)培养HepG2细胞建立具有IR的细胞模型，测定培养液中葡萄糖含量及细胞内糖原含量作为鉴定指标；(2)用Western blot检测胞内糖原合酶(GS)和蛋白激酶B(PKB)蛋白水平；(3)用磷脂酰肌醇3激酶(P13K)抑制剂Wortmannin(WT)探讨其对胰岛素信号通路的影响；(4)观察AA是否对PA引起的IR有防治作用。结果 (1)0．20mmol／L PA或川培养HepG2细胞36h后，培养液中葡萄糖含量极显著增高，细胞内糖原含量极显著减少；(2)高浓度PA使磷酸化的PKB(P-Ser473)蛋白水平显著减少，磷酸化的糖原合酶(P-Ser641 GS)蛋白水平极显著增加；(3)WT使对照组GS活性及胞内糖原含量极显著减少，HI组和PA组胞内糖原含量均无统计学差异，但各实验组PKB活性都极显著减少；(4)PA AA组培养液中葡萄糖含量显著低于PA组，GS和PKB活性及胞内糖原含量显著增加。结论 高浓度PA或HI培养HepG2细胞能够诱导IR，其机制可能是其引起胰岛素信号传递途径中自PKB下游到GS之间的信号通路受阻所致。AA能改善PA引起的IR。     

Ultrafast-acting insulins: state of the art

Optimal coverage of prandial insulin requirements remains an elusive goal. The invention of rapid-acting insulin analogs (RAIAs) was a big step forward in reducing postprandial glycemic excursions in patients with diabetes in comparison with using regular human insulin; however, even with these, the physiological situation cannot be adequately mimicked. Developing ultrafast-acting insulins (UFIs)-showing an even more rapid onset of action and a shorter duration of action after subcutaneous (SC) administration-is another step forward in achieving this goal. The need for UFIs has been gradually recognized over the years, and subsequently, a number of different approaches to cover this need are in clinical development. A rapid increase in circulating insulin levels can be achieved by different measures: modification of the primary structure of insulin molecule (as we know from RAIAs), addition of excipients that enhance the appearance in the monomeric state post-injection, or addition of enzymes that enable more free spreading of the insulin molecules in the SC tissue. Other measures to increase the insulin absorption rate increase the local blood flow nearby the insulin depot in the SC tissue, injecting the insulin intradermally or applying via another route, e.g., the lung. The development of these approaches is in different stages, from quite early stages to nearing market authorization. In time, daily practice will show if the introduction of UFIs will fulfill their clinical promise. In this review, the basic idea for UFIs will be presented and the different approaches will be briefly characterized.     

Reduction of postprandial glycemic excursions in patients with type 1 diabetes: a novel human insulin formulation versus a rapid-acting insulin analog and regular human insulin

Background:

Evaluation of postprandial glycemic excursions in patients with type 1 diabetes with three prandial insulins: VIAject™ (Linjeta™), an ultra-fast insulin (UFI); insulin lispro (LIS); and regular human insulin (RHI).

Methods:

After stabilization of preprandial glycemia, 18 patients received a subcutaneous injection with an individualized insulin dose prior to a meal.

Results:

Injection of UFI resulted in a more rapid insulin absorption than with either LIS or RHI (time to half-maximal insulin levels: 13.1 ± 5.2 vs 25.4 ± 7.6 and 38.4 ± 19.5 min; p = .001 vs LIS and p < .001 vs RHI, LIS vs. RHI p < .001). Maximal postprandial glycemia was lower with UFI (0–180 min; 157 ± 30 mg/dl; p = .002 vs RHI) and LIS (170 ± 42 mg/dl; p = .668 vs RHI) than after RHI (191 ± 46 mg/dl; RHI vs LIS p = .008). The difference between maximum and minimum glycemia was smaller with UFI (70 ± 17 mg/dl) than with either RHI (91 ± 33 mg/dl; p = .007 vs UFI) or LIS (89 ± 18 mg/dl; p = .011 vs UFI). Also, the area under the blood glucose profile was lower with UFI than with RHI (0–180 min; 21.8 ± 5.8 vs 28.4 ± 7.6 g·min/dl; p < .001).

Conclusions:

The rapid absorption of UFI results in a reduction of postprandial glycemic excursions.     

Insulin Pump Therapy: What Is the Evidence for Using Different Types of Boluses for Coverage of Prandial Insulin Requirements?

Bolus infusion of insulin along with a meal is a standard procedure with continuous subcutaneous insulin infusion. Modern insulin pumps allow applying this bolus in four different ways: infusion of the total dose at once or splitting the dose into two boluses, infusion of a part of the bolus in the usual manner plus infusion of the other part over a prolonged period of time (with a higher infusion rate than the basal rate), or infusion of the total dose in the form of an elevated basal rate. Depending on the composition of the given meal and its glycemic index, this is an attempt to match the circulating insulin levels to the rate of glucose absorption from the gut in order to minimize postprandial glycemic excursions. However, in the framework of evidence-based medicine, the benefits of this approach should be proven in appropriately designed clinical studies. Performance of meal-related studies requires careful attention to many aspects in order to allow meaningful evaluation of a given intervention (i.e., type of bolus). Critical evaluation of the clinical experimental studies and the one clinical study published about the impact of different types of boluses on postprandial metabolic control revealed fundamental shortcomings in study design and performance in these studies. Insufficient establishment of comparable preprandial glycemia and insulinemia on the different study days within and between the patients studied is one key aspect. Therefore, the recommendation made in most of these studies (i.e., use of dual-wave bolus) has to be accepted with care, until we have better evidence.     

Absorption kinetics and action profiles of mixtures of short-and intermediate-acting insulins

Summary The effects of mixing short- and intermediate-acting insulins (lente and NPH) on plasma insulin levels and action profiles, assessed by the euglycaemic clamp technique, were studied in 10 volunteers. Four protocols were used: (1) comparison between two semi-synthetic human soluble insulins in seven subjects (0.22 IU/kg); (2) assessment of insulin levels and action profiles of lente insulin in six subjects and of NPH insulin in five subjects (0.33 IU/kg); (3) comparison between mixtures of soluble with lente insulin and soluble with NPH insulin, administered immediately after mixing, in eight subjects (0.55IU/kg, 40% short-acting); (4) same mixtures, administered 2 days after preparation, in seven subjects. No differences in insulin levels and action profiles during the first 4 h after injection were found between both short-acting insulins and the soluble + NPH insulin mixtures. After the administration of NPH insulin, plasma insulin levels rose slightly faster in comparison with lente insulin, with no significant differences between the action profiles for either insulin. Onset of action was delayed after soluble + lente insulin, both when administered immediately after mixing and to a greater extent when stored for 2 days before administration. After the latter procedure, the onset of action was markedly retarded and only slightly faster than after lente insulin alone.We conclude, therefore, that mixing soluble with NPH insulin in a ratio of 2:3 does not affect the absorption kinetics of soluble insulin, whereas the onset of action is delayed when soluble is combined in the syringe with lente insulin, even when administered immediately after mixing.     

A review of a family of ultra-rapid-acting insulins: formulation development

This review summarizes the clinical development of a family of ultra-rapid-acting recombinant human insulin formulations. These formulations use ethylenediaminetetraacetic acid (EDTA) to chelate zinc and thereby destabilize insulin hexamers. In addition, insulin monomer surface charges are chemically masked with citrate to prevent reaggregation. The first phase 1 trials were performed using BIOD-090, an acidic 25 unit U/ml insulin formulation, which contained disodium-EDTA (NaEDTA). When compared with regular human insulin (RHI) and/or insulin lispro in multiple phase 1 studies, BIOD-090 consistently showed more rapid absorption and/or onset of action. A standard meal challenge study also demonstrated improved postprandial glucose profiles associated with BIOD-090. However, increased patient exposure in larger phase 3 trials showed that this formulation was associated with an increased incidence of local injection site reactions, most commonly pain. A next generation formulation, BIOD-100, contained the same excipients as a standard insulin concentration of 100 U/ml. BIOD-100 maintained an ultra-rapid action profile and was associated with modest but significantly improved toleration when compared with BIOD-090. In order to further improve toleration, the hypothesis that NaEDTA contributed to discomfort by chelating endogenous calcium was tested by either substituting calcium-EDTA for NaEDTA or by adding calcium chloride to the NaEDTA formulation. These calcium formulations essentially eliminated the excess discomfort associated with BIOD-090 but were associated with less optimal pharmacokinetic profiles in humans. Recent efforts have succeeded in developing ultra-rapid-acting human insulin formulations with acceptable injection site toleration by optimizing concentrations of calcium (BIOD-125) and with the use of magnesium sulfate to mitigate discomfort (BIOD-123). Similar formulation technology has also been shown to accelerate absorption of insulin analogs in animal models.     

Effect of storage temperature of insulin on pharmacokinetics and pharmacodynamics of insulin mixtures injected subcutaneously in subjects with Type 1 (insulin-dependent) diabetes mellitus

Summary These studies were undertaken to assess the influence of storage temperature of insulin vials on pharmacokinetics and pharmacodynamics of a mixture of lente insulin (Monotard HM) and regular insulin (Actrapid HM) injected subcutaneously. Seven subjects with Type 1 (insulin-dependent) diabetes mellitus were studied twice after overnight normalization of plasma glucose. A mixture of lente insulin (0.22 U/kg) and regular insulin (0.11 U/kg) was prepared from insulin vials kept either refrigerated (4 °C) or at room temperature (18 °C) and injected subcutaneoulsy (abdomen). Euglycaemia was maintained for the following 16 h by glucose infusion at variable rate. With refrigerated insulin, the plasma free insulin peak was greater (53±5 versus 45±6 mU/l) and occurred earlier (2.5±0.2 versus 6±0.3 h), and the glucose infusion rate showed a greater (16.5±1.2 versus 14.5±0.9 mol·kg^–1·min^–1) and earlier peak (3.2±0.2 versus 6±0.4 h) as compared to that occurring with the non-refrigerated insulin (p<0.05). However, 6 h after insulin injection, both plasma free insulin and glucose infusion rate were 30% lower with the mixture of refrigerated as compared to that of non-refrigerated insulin (p<0.05). In contrast, when NPH-insulin (Protaphane HM) was mixed with regular insulin and injected in 4 out of the 7 diabetic patients, the storage temperature of insulin vials had no effect on the pharmacokinetics and pharmacodynamics of the mixture. Thus, the storage temperature of insulin vials profoundly influences the effects of the mixture lente/regular insulin, but does not affect the pharmacokinetics and pharmacodynamics of the mixture NPH/regular insulin.     

Immunogenicity of recombinant DNA human insulin

Summary We postulated that human insulin of recombinant DNA origin would be a poor immunogen and might prove to be less immunogenic than purified pork insulin. Results are reported for 100 diabetic subjects not previously treated with insulin. Individuals completed the first 12 months of a clinical trial of human insulin of recombinant DNA origin. These patients are contrasted with 121 similar individuals who are taking part in a trial of purified pork insulin. Prior to therapy, species-specific binding of ¹²⁵I human insulin and pork insulins and insulin bound to antibody were undetectable in all individuals. In patients treated with human insulin of recombinant DNA origin, binding of ¹²⁵I human insulin increased to 10±1.2% at 12 months versus increases in binding of ¹²⁵I pork insulin in pork insulin-treated patients to 12.6±1.4% (NS). Mean percentages of species-specific binding tended to reach a plateau in the human insulin-treated group but continued to increase in the pork insulin group (p<0.001). Median bound values were nil throughout in patients treated with human insulin, but increased to 52 mU/l in the pork insulin group with significantly less bound insulin seen in the former group at all visits (p<0.001). The percentage of individuals who remained antibody free at 12 months, as indicated by bound insulin, was 56% in the human insulin-treated patients and 40% in the patients treated with pork insulin (p<0.01). In 11 out of 55 individuals who initially developed detectable insulin antibodies while being treated with human insulin, bound insulin levels later became undectable compared with three out of 77 individuals in the pork insulin-treatment group (p<0.005). Human insulin of recombinant DNA origin is less immunogenic than purified pork insulin. Level of antibodies in patients treated with human insulin of recombinant DNA origin reached a plateau after 6 months and antibody levels often tended subsequently to decrease below detection limits.     

Isoimmunization of man by recrystallized human insulin

Summary Ten non-diabetic psychiatric patients, who had not previously been treated with insulin, underwent insulin coma therapy by recrystallized, non-monocomponent human insulin in neutral solution. The treatment was given for 1–3 months, in maximum doses of 96–196 units daily. Several patients formed insulin antibodies. The cause of the antibody formation is discussed. The presence of small quantities of the a-fraction in the insulin is assumed to be of importance in the insulin antibody formation.

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Isoimmunisation des Menschen mit rekristallisiertem menschlichen Insulin

Zusammenfassung Zehn nicht-diabetische psychiatrische Patienten, die vorher nicht mit Insulin behandelt worden waren, wurden einer Insulinkomatherapie mit einem nicht-monokomponentartigen Humaninsulin in neutraler Lösung unterzogen. Die Behandlung wurde 1–3 Monate lang mit Maximaldosen von 96–196 E täglich durchgeführt. Mehrere Patienten erzeugten Insulinantikörper. Die Ursache der Antikörperentstehung wird diskutiert. Die Anwesenheit kleiner Mengen der a-Fraktion des Insulins könnte für die Insulinantikörperbildung von Bedeutung sein.

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Isoimmunisation de l'homme par de l'insuline humaine recristallisée

Résumé Dix patients non-diabétiques, atteints de maladie psychiatrique, n'ayant pas été traités auparavant par l'insuline, ont subi une thérapeutique par coma insulinique avec de l'insuline humaine contenant plusieurs fractions, recristallisée et mise en solution neutre. Le traitement a été administré pendant 1–3 mois, à des doses maximales de 96–196 unités par jour. Plusieurs patients ont élaboré des anticorps anti-insuline. La cause de la formation d'anticorps est discutée. La présence de petites quantités de la fraction-a dans l'insuline semble avoir une importance dans la formation des anticorps anti-insuline.