Near visual acuity: a simple measure of practical significance in insulin-treated diabetic patients.

The value of measuring near visual acuity as a predictor of loss of independence in administering insulin and monitoring blood or urine glucose has been assessed in 110 insulin-treated diabetic patients. Near visual acuity was simple to measure in the clinic setting, and correlated well with 6 m acuity. Fourteen patients depended on an assistant either to draw up the correct dose of insulin (n = 12), inject the insulin (n = 7) or to monitor blood or urine glucose (n = 12). Of these 14 patients only one, who was demented, had near visual acuity better than N.12. Two other patients had near visual acuity N.12 or worse and yet were independent of help. One had severe visual impairment and used a pen-injector and a meter with speech synthesizer, and the other had near visual acuity of N.12. Impairment of near visual acuity to N.12 or worse is associated with loss of independence in insulin-treated diabetes. Measurement of near visual acuity could be useful in predicting independence of insulin-treated patients.     

模拟缺血再灌注后心肌细胞的胰岛素抵抗现象

目的准确评价缺血再灌注心肌的胰岛素敏感性及其时相规律，为临床干预提供依据。方法建立成年大鼠心肌细胞模拟缺血60min再灌注模型，应用同位素示踪技术观察不同浓度（0IU／L、0．01IU／L、20IU／L）胰岛素刺激大鼠心肌细胞的葡萄糖摄取效应。结果缺血60min后再灌注15min和60min，心肌细胞活性比率无明显降低（P〉0．05）。胰岛素能促进各组心肌细胞的葡萄糖摄取，并呈剂量依赖性。缺血再灌注15min组和再灌注60min组心肌细胞胰岛素刺激的葡萄糖摄取较对照组均明显降低（P〈0．05）。再灌注60min组心肌细胞胰岛素刺激的葡萄糖摄取较再灌注15min组明显增加（P〈0．05）。结论缺血60min后，再灌注心肌细胞保留了对胰岛素的反应性，同时，再灌注心肌细胞发生明显的急性胰岛素抵抗，再灌注初期尤为严重。急性胰岛素抵抗很可能是缺血再灌注心肌损伤的又一重要机制。     

胰岛素和睾酮对Ishikawa细胞葡萄糖转运蛋白4表达的影响

目的探讨胰岛素(INS)和睾酮(T)对多囊卵巢综合征(PCOS)子宫内膜腺上皮细胞生长的影响和葡萄糖转运蛋白4(GLUT4)表达的调节机制。方法体外培养Ishikawa细胞,予不同浓度INS(90、60、30、3、0.3 U/L)或T(10-3、10-4、10-5、10-6、10-7mmol/ml)刺激Ishikawa细胞48 h,MTT法检测INS、T对Ishikawa细胞生长的作用;免疫细胞化学检测GLUT4蛋白在Ishikawa细胞定位表达;分别以30 U/L INS和10-5mmol/ml T刺激Ishikawa细胞24和48 h,逆转录聚合酶链反应(RT-PCR)方法测定INS和T对Ishikawa细胞GLUT4 mRNA表达的影响。结果(1)不同浓度的INS均可促进Ishikawa细胞的生长,随着INS浓度的增加,INS促进Ishikawa细胞生长作用越强,INS浓度自0.3~30 U/L时,Ishikawa细胞生长依次加强,与对照组相比均有显著性差异(P<0.01)。INS浓度达60、90 U/L时,细胞生长状况与INS浓度为30 U/L相似。不同浓度的T均可抑制Ishikawa细胞的生长,随着T浓度的增加,T抑制Ishikawa细胞生长作用越明显。T浓度自10-7、10-6、10-5mmol/ml,Ishikawa细胞生长依次减弱,与对照组相比均有显著性差异(P<0.01,P<0.05),T浓度达10-4、10-3mmol/ml时,细胞生长抑制状况与T浓度10-5mg/ml相似。(2)GLUT4蛋白,定位表达于Ishikawa细胞的细胞浆内。(3)Ishikawa细胞中GLUT4 mRNA表达,在INS组和T组均较对照组减弱(P<0.01,P<0.05),INS组比T组减弱更明显(P<0.05),且INS和T作用24和48 h GLUT4 mRNA表达无显著性差异(P>0.05)。结论不同浓度INS和T均可影响Ishikawa细胞生长,并降低GLUT4 mRNA的表达,推测PCOS高胰岛素、高雄激素血症的病理生理特性有可能影响子宫内膜的代谢过程,与子宫内膜的病变相关。     

Metabolic Characterization of Nondiabetic Severely Obese Patients Undergoing Roux-en-Y Gastric Bypass: Preoperative Classification Predicts the Effects of Gastric Bypass on Insulin–Glucose Homeostasis

Introduction Obese individuals may have normal insulin–glucose homeostasis, insulin resistance, or diabetes mellitus. Whereas gastric bypass cures insulin resistance and diabetes mellitus, its effects on normal physiology have not been described. We studied insulin resistance and β-cell function for patients undergoing gastric bypass. Methods One hundred thirty-eight patients undergoing gastric bypass had fasting insulin and glucose levels drawn on days 0, 12, 40, 180, and 365. Thirty-one (22%) patients with diabetes mellitus were excluded from this analysis. Homeostatic model of assessment was used to estimate insulin resistance, insulin sensitivity, and β-cell function. Based on this model, patients were categorized as high insulin resistance if their insulin resistance was >2.3. Results Body mass index did not correlate with insulin resistance. Forty-seven (34%) patients were categorized as high insulin resistance. Correction of insulin resistance for this group occurred by 12 days postoperatively. Sixty (43%) patients were categorized as low insulin resistance. They demonstrated an increase of β-cell function by 12 days postoperatively, which returned to baseline by 6 months. At 1 year postoperatively, the low insulin resistance group had significantly higher β-cell function per degree of insulin sensitivity. Conclusions Adipose mass alone cannot explain insulin resistance. Severely obese individuals can be categorized by degree of insulin resistance, and the effect of gastric bypass depends upon this preoperative physiology.     

危重新生儿血糖、胰岛素及皮质醇的初步研究

本文通过对３８例危重新生儿血糖、胰岛素及皮质醇的研究，发现在危重新生儿组血糖与皮质醇的均植高于对照组（分别为Ｐ＜０．０５与Ｐ＜０．０１），且危重新生儿组高血糖的发生率（３４．２％）也明显高于对照组（６％），而血胰岛素在各组之间无显著差异（Ｐ＞０．０５），研究表明危重新生儿易发生高血糖，其发生的机理与血皮质醇的升高及新生儿胰β细胞功能不良有关。     

Growth promoting and metabolic activity of the human insulin analogue [Gly,Arg,Arg]insulin (HOE 901) in muscle cells

[Gly^A21,Arg^B31,Arg^B32]insulin (HOE 901) represents a biosynthetic human insulin analogue that, due to its isoelectric point, precipitates at neutral tissue pH leading to a retarded absorption rate and a corresponding longer duration of action. In the present investigation we have evaluated the growth promoting and metabolic activity of this analogue in muscle tissue using exponentially growing H9c2 cardiac myoblasts and adult rat ventricular cardiomyocytes. Equilibrium binding studies of ¹²⁵I-labelled IGF-I (insulin-like growth factor I) to differentiating myoblasts revealed the presence of 7×10³ IGF-I receptors per cell. In contrast, no specific binding of insulin could be detected. Competition binding experiments showed a slightly higher affinity of HOE 901 for the IGF-I receptor when compared to regular human insulin with IC₅₀ (half-inhibitory concentration) values of 70 and 101 nM, respectively. However, the supermitogenic insulin analogue [Asp^B10]insulin competed significantly more efficiently for IGF-I binding (IC₅₀: 44 nM). Maximum growth promoting activity of the peptides was then determined in serum-starved myoblasts by an incubation with the peptides (5×10⁻⁷ M) for 16 h in the presence of [³H]thymidine. [Asp^B10]Insulin produced a stimulation of DNA synthesis (about 3-fold) which was comparable to the effect of IGF-I and significantly (P<0.005) higher than the effect of HOE 901 with the latter being essentially equipotent to native insulin. Comparable results were obtained at lower concentrations of the peptides (10⁻⁹ to 10⁻⁸ M). Metabolic activity of HOE 901 was determined by measuring the dose-dependent stimulation of 3-O-methylglucose transport in adult cardiomyocytes. Maximum transport stimulation was identical for insulin and HOE 901 with EC₅₀ (half-effective concentration) values of 0.7×10⁻¹⁰ and 1.9×10⁻⁹ M, respectively. We concluded that the IGF-I receptor-mediated growth promoting activity of HOE 901 in muscle cells and the maximal metabolic activity of this analogue are not different from those of native human insulin. It is suggested that differential interaction with IGF-I receptors significantly contributes to the action profile of insulin analogues.     

Pharmacokinetics of insulin following intravenous and subcutaneous administration in canines

Studies were conducted to examine the absorption and disposition kinetics of insulin in dogs following intravenous (IV) and subcutaneous (SC) administration of commercial preparations. After IV and SC dosing, the plasma levels were described by models which considered basal insulin level contributions. Intersubject variation in the disposition kinetics was small with half-lives of 0.52 +/- 0.05 h and total body clearances of 16.21 +/- 2.08 ml min-1 kg-1. Calculated insulin plasma secretion rates in the canines were 14.4 +/- 3.3 mUh-1 kg-1. Following SC injection of regular insulin, the rate and extent of absorption were noted to be quite variable. The absorption process appeared first-order with half-life values of 2.3 +/- 1.3 h and extents of absorption of 78 +/- 15 per cent with a range of 55-101 per cent. Insulin absorption from SC NPH preparations was evaluated as being composed of two zero-order release phases, a rapid and a slow release phase. With a dose of 1.65 U kg-1, the rapid release phase had an average duration of 1.5 h and a rate of 580 +/- 269 mUh-1 (4.2 per cent of dose) while the slow phase had a zero-order rate of 237 +/- 92 mU h-1 which continued beyond 12 h. The extent of absorption from the NPH preparation was 23.6 +/- 5.1 per cent and was significantly lower than that for the regular injection.     

胰岛素抵抗性高血压大鼠α1肾上腺素受体亚型的改变

目的和方法：用高糖喂养复制胰岛素抵抗性高血压（ｉｎｓｕｌｉｎ－ｒｅｓｉｓｔａｎｔｈｙｐｅｒｔｅｎｓｉｏｎ，ＩＲＨ）大鼠模型，用放射配体结合实验和离体左心房及主动脉收缩功能实验，观察ＩＲＨ大鼠α１肾上腺素受体（α１－ａｄｒｅｎｏｃｅｐｔｏｒ，α１－ＡＲ）及其３种亚型在心脏和主动脉的改变。结果和结论：ＩＲＨ大鼠与同龄ＳＤ大鼠相比：（１）心脏α１－ＡＲ密度下降４８％（Ｐ＜００５），而介导的正性变力效应不变。（２）心脏α１－ＡＲ３种亚型占α１－ＡＲ总数的比例和在介导心脏正性变力效应中的作用表现为α１Ｂ－ＡＲ增加，α１Ｄ－ＡＲ减少，而α１Ａ－ＡＲ不变。（３）介导主动脉收缩的α１－ＡＲ及各亚型对激动剂的敏感性及最大收缩效应均无明显改变。     

地塞米松对肺癌切除术病人血清过氧化脂质胰岛素皮质醇的影响

４０例肺癌切除术病人，随机分为对照（Ｓ）组和地塞米松（Ｓ－Ｄ）组，采用氯胺酮－安氟醚静吸复合麻醉，对血清中过氧化脂质、胰岛素和皮质醇进行了初步观察。结果表明，血清过氧化脂质Ｓ－Ｄ组于手术毕显著低于Ｓ组（Ｐ〈０．０５）；血清胰岛素两组间没有统计学差异；血清皮质醇Ｓ－Ｄ组于气管插管后显著高于Ｓ组（Ｐ〈０．０５）。作者认为肺癌切除术病人术前给地塞米松可有效地降低血清中过氧化脂质含量，利于维护脏器功能。