Receptor-recycling model of clearance and distribution of insulin in the perfused mouse liver

Summary After perfusion of mouse livers with A₁₄-¹²⁵I-insulin for designated intervals, an acid-wash technique was employed to separately measure the surface-bound (X_s) and intracellular (X_i) A₁₄-¹²⁵I-insulin, as well as intracellular degradation products (X_deg) of labelled insulin. From the perfusate concentrations (C_p) of A₁₄-¹²⁵I-insulin, the apparent intrinsic hepatic clearance of labelled insulin at a high dose (0.2 nmol/l) was shown to be 60% smaller than that at a low dose (0.018 nmol/l), indicating that the cellular uptake of insulin is remarkably nonlinear at the concentration range examined. From the time courses of C_p, X_s, X_i and X_deg, the hepatic insulin disposition was shown to be largely accounted for by the receptor-mediated endocytosis. The observed data at the low dose were analysed to estimate biochemical parameters, (i.e., total receptor number, endocytotic rate constant and intracellular degradation rate constant) according to receptor-recycling and non-receptor-recycling models, using a computer-aided optimization procedure. The receptor-recycling model could not only adequately explain the C_p, X_s, X_i and X_deg at the low dose, but also predict the C_p at the high dose. On the other hand, a non-receptor-recycling model, in which recycling of receptors was not assumed, could also explain the observed data at the low dose, but failed to predict the C_p at the high dose, indicating that the receptor recycling process is necessary to explain the hepatic insulin clearance at high insulin concentrations, at which hepatic insulin clearance should be limited by the rate of receptor recycling. However, the applicability of our model might be limited within the physiologic insulin concentrations, because of the negative co-operativity of insulin-receptor interaction and a high-capacity, non-degradative and more rapidly recycling pathway for receptors that may occur at high concentrations of insulin. In conclusion, we have developed a mathematical model of hepatic insulin clearance and distribution under physiological conditions, including receptor binding, receptor-mediated endocytosis and receptor recycling, which has been so far demonstrated using isolated hepatocytes.     

胰岛素基础--大剂量方案治疗青春期1型糖尿病儿童的疗效观察

目的：观察胰岛素基础—大剂量注射方案治疗青春期1型糖尿病儿童的临床疗效。方法：采用胰岛素基础—大剂量治疗方案4次／d(睡前注射中效，三餐前注射短效)治疗4例青春期糖尿病患儿6月。结果：4例患儿慢性高血糖症得以控制，空腹及餐后血糖水平接近正常，糖化血红蛋白(HbA1α)基本恢复正常，酮症酸中毒发生减少。结论：胰岛素基础—大剂量方案治疗能够控制青春期糖尿病血糖水平。     

GAD-Ab、ICA和IAA联合检测对成人隐匿性自身免疫性糖尿病的诊断价值（附138例分析）

目的 评价血清谷氨酸脱羧酶抗体(GAD—Ab)、胰岛细胞抗体(ICA)和胰岛素自身抗体(IAA)联合测定对成人隐匿性自身免疫性糖尿病(LADA)的诊断价值。方法 利用ELISA法测定138例临床诊断为2型糖尿病患者及46例健康者的血清GAD—Ab、ICA和IAA，并比较抗体阳性和阴性患者的临床特征。结果 临床诊断为2型糖尿病患者GAD-Ab和ICA的阳性率分别为20．3％和11．6％，与对照组比较差异有显著性(X^2=8．528，P=0．003；X^2=5．841，P=0．016)；IAA的阳性率8．0％。与对照组比较无显著性差异(X^2=1．902，P=0．168)。抗体阳性患者血清C肽水平较低。结论 胰岛自身抗体联合检测可提高LADA患者的检出率；LADA患者胰岛储备功能较差。     

胰岛素超细化处理及其吸入给药系统的基础研究

综述胰岛素超细化处理方法及其吸入给药系统基础研究的最新进展，着重介绍超临界反溶剂过程用于胰岛素超细化处理的研究成果。     

针灸对胰岛素抵抗影响研究的概况

本文系统回顾了近年来胰岛素抵抗的针灸治疗的研究概况。发现针灸在调节高血压、糖尿病、中风、肥胖症等的胰岛素抵抗方面有显著的疗效．对于胰岛素抵抗可致的各方面的病理生理改变均有不同程度改善。     

转化生长因子-β1和胰岛素对人鼻中隔软骨细胞增殖和分化影响的研究

目的 了解转化生长因子-β1(transforminggrowth factor-beta 1,TGF-β1)和胰岛素对人鼻中隔软骨细胞增殖和分化的影响。方法 体外培养人鼻中隔软骨细胞,采用四甲基偶氮唑蓝(MTT)代谢和35S-Na2SO4掺入的检测比较不同浓度TGF-β1和胰岛素对人鼻中隔软骨细胞的增殖以及软骨基质蛋白多糖合成的影响,观察TGF-β1和胰岛素对软骨细胞表型的影响。结果在15％血清的培养条件下,TGF-β1和胰岛素均能显著促进软骨细胞增殖,且在各自一定的浓度范围内呈量效关系,联合作用效果累加;TGF-β1、TGF-β1和胰岛素联合作用促使软骨基质蛋白多糖的合成量明显提高;TGF-β1使传代软骨细胞去分化提前。结论一定浓度的TGF-β1、胰岛素和TGF-β1 胰岛素对体外培养的人鼻中隔软骨细胞具有显著的促增殖作用。     

2001年—2003年第1季度北京地区门诊患者降血糖用药动态分析

目的 :了解北京地区糖尿病患者的用药需求 ,并对降血糖药物进行分析。方法 :采用《医院处方分析》课题 (北京地区 )2 0 0 1年～ 2 0 0 3年每年第 1季度门诊降血糖用药的处方数据进行比较。结果与结论 :通过统计 ,北京地区糖尿病患者人数不断增多 ,且人们更多选用了新型降糖药。在临床应用中 ,口服制剂以磺酰脲类用量居主导地位 ,而α-葡萄糖苷酶抑制剂用量逐年上升 ;使用基因合成人胰岛素较动物胰岛素的用量逐年增多 ,为控制糖尿病用药及合理应用提供了依据     

2型糖尿病患者血清肿瘤坏死因子和唾液酸联合检测的临床意义

目的　探讨血清 TNF和 SA含量在 2型糖尿病患者发生和发展中作用。方法　分别应用放免法和化学法测定 88例 2型糖尿病患者血清 TNF和 SA含量 ,并与 35名正常人作对照。结果　 2型糖尿病患者血清TNF、SA含量则显著地高于正常人组 (P<0 .0 1) ,且与胰岛素水平呈明显的正相关 (r=0 .6 82 5 ,0 .6 2 6 3,P<0 .0 1)。结论　测定 2型糖尿病患者血清中 TNF、SA含量的变化对其观察病情的变化具有重要的临床价值     

Postprandial glycaemia after regular and lispro insulin in children and adolescents with diabetes

We compared the postprandial blood glucose (BG)-levels following preprandial regular insulin or lispro insulin before and after eating in adolescents with diabetes. Lispro is a rapidly absorbed insulin analogue. Lispro insulin injected immediately before breakfast reduced the postprandial BG-rise significantly compared to the 20 min preprandially administered regular insulin (P<0.01). Postprandial lispro injection resulted in similar BG values as the standard treatment with regular insulin 20 min preprandially. Conclusion Lispro insulin injected immediately before the meal leads to lower postprandial BG levels and seems to be an option for teenagers who use multiple preprandial insulin injections. Postprandial lispro administration could be a benefit in certain situations since it resulted in similar BG values to preprandial regular insulin. Received: 13 March 1997 / Accepted: 26 May 1997     

Ⅱ型糖尿病和高血压患者血液动力学改变的相关因素分析

目的：探讨糖病和高血压血管并发症的发生机理。方法：分别测定高血压（ＨＴ）组、Ⅱ型糖尿病（ＮＩＤ－ＤＭ）组及Ⅱ型糖尿病合并高血压组和对照组的胰岛素水平、血脂、心脏彩超和血液流变学指标。结果：３个试验组的周围总阻（ＴＰＲ）、甘油三酯（ＴＧ）和胰岛素面积（ＩｎｓＳ）均明显增高,其中ＨＴ组和ＮＩＤＤＭ合并ＨＴ组的左室收缩期峰值室壁应力（ＰＳＳ）也明显增高：ＮＩＤＤＭ合并ＨＴ组ＩｎｓＳ明显高于其他三组,三试