扩展高胰岛素-正葡萄糖钳夹技术的建立

目的建立扩展高胰岛素-正葡萄糖钳夹技术.方法应用扩展葡萄糖钳夹技术(即联合葡萄糖钳夹、3-3H标记葡萄糖示踪技术及间接测热技术)对9例正常体重、正常糖耐量者进行方法学研究.结果(1)在优势浓度胰岛素、血浆葡萄糖稳定在正常水平状态下肝糖产生完全被抑制,未见到升糖激素(皮质醇、生长激素、胰高血糖素)显著兴奋及内源性胰岛素释放.(2)扩展高胰岛素-正葡萄糖钳夹稳态期,胰岛素介导的机体葡萄糖利用率(葡萄糖消失率)较基础状态显著增加[(5.86±0.65)mg*kg-1*min-1比(2.45±0.15)mg*kg-1*min-1,P＜0.01],并以糖原合成为主;脂肪氧化被显著抑制,游离脂肪酸浓度显著下降.结论扩展高胰岛素-正葡萄糖钳夹技术已成功建立;在外源性胰岛素-葡萄糖代谢的稳定状态下,机体对葡萄糖利用显著增加,脂肪分解显著减少.     

两步法高胰岛素-正常葡萄糖钳夹技术的建立

目的　建立两步法高胰岛素 正常葡萄糖钳夹技术。　方法　应用两步法高胰岛素-正常葡萄糖钳夹术(第一阶段胰岛素输注速率为 30 mU·m-2 ·min-1,第二阶段为 120 mU·m-2 ·min-1),评估10名健康女性志愿者的胰岛素敏感性,同时监测钳夹试验过程中循环血内源性升糖激素(胰高血糖素、皮质醇、生长激素)和游离脂肪酸(FFA)浓度变化。　结果　(1)两步法高胰岛素 正常葡萄糖钳夹术第一阶段(60~90 min)和第二阶段(150~180 min) 稳态血胰岛素分别维持在(46±7)mU/L和(218±27)mU/L,稳态葡萄糖利用率分别为(7.2±1.4)mg·kg-1·min-1和(13.1±1.2)mg·kg-1·min-1;(2)钳夹试验过程中,血清胰高血糖素、皮质醇和 FFA水平较基础值均有显著下降,而生长激素和C肽水平无明显改变。　结论　成功建立了两步法高胰岛素 正常葡萄糖钳夹术;钳夹试验过程中高浓度的胰岛素抑制了胰高血糖素、皮质醇的分泌,并减少脂肪分解。     

不同浓度胰岛素输注对胰岛素钳夹大鼠糖代谢的影响

大鼠正糖钳夹技术(Euglycemic clamp technique)是近年来国外广泛应用胰岛素抵抗动物模型的实验研究。国内虽有个别报道,但其钳夹术是在麻醉及手术状态下,且未作糖代谢研究。我们设计了清醒大鼠胰岛素钳夹模型,用6,6-D_2葡萄糖作非放射性示踪剂,给予三种浓度胰岛素输注,观察了大鼠糖代谢及血浆游离脂肪酸(FFA)的改变。     

小鼠扩展胰岛素钳夹术中糖代谢的变化

目的建立小鼠扩展胰岛素钳夹技术并观察其体内糖代谢的变化。方法分别采用[3-^3H]葡萄糖和2-脱氧-^3H葡萄糖（2-DOG）作为示踪剂,建立自由状态下小鼠正糖-高胰岛素钳夹技术,并观察其体内糖代谢的动态改变。结果在钳夹稳定状态,血糖稳定在基础水平（7.0±1.3mmol/L）,在高血浆胰岛素水平下,血浆FFA明显抑制（从1.45±0.15到0.45±0.08mmol/L,P〈0.01）。葡萄糖输注率为46.7±4.7mg·kg^-1·min^-1,葡萄糖清除率为11.2±0.6mg·kg^-1·min^-1,肝糖产生被完全抑制,骨骼肌葡萄糖摄取率为20.9±2.5μmol·100g^-1·min^-1,而TG和TC浓度较钳夹前明显降低（P均〈0.01）。平均血糖变异系数为5.19%,平均GIR变异系数为9%。结论采用上述示踪剂建立的小鼠扩展胰岛素钳夹技术,能准确评价小鼠机体胰岛素敏感性,同时能动态反映体内糖代谢变化。     

非胰岛素依赖型糖尿病病人的胰岛素抵抗情况如何?

胰岛素钳夹技术(insulin clamp technique)已广泛用于体内胰岛素作用及抵抗的定量研究。但过去只注重于观察稳定胰岛素状态下的总葡萄糖利用率,而忽略了总葡萄糖利用率是由基础状态的糖摄取及胰     

多不饱和脂肪酸对大鼠肝脏甘油三酯蓄积和胰岛素抵抗的影响

目的研究短期多不饱和脂肪酸增高对大鼠肝脏TG含量和胰岛素抵抗的影响。方法给大鼠输注脂肪乳,行清醒高胰岛素-正血糖钳夹试验,观察脂肪乳对葡萄糖利用和肝葡萄糖产生的影响。结果脂肪乳使血浆FFA和TG升高,使肝脏TG和肝葡萄糖产生亦明显升高,钳夹状态葡萄糖利用显著降低。结论短期多不饱和脂肪酸增高可引起肝脏TG蓄积和胰岛素抵抗。     

长效胰岛素类似物葡萄糖钳夹研究结果分析

高胰岛素-正葡萄糖钳夹技术通过同时外源性输注胰岛素和葡萄糖,将血糖维持在设定的稳态,最初用于评价机体的胰岛素敏感状况,近年来也用于评估胰岛素制剂的药理学特点,被公认为是评价胰岛素作用的"金标准".     

大鼠清醒和麻醉状态下胰岛素钳夹实验结果的比较

目的　探讨苯巴比妥麻醉对正常大鼠体内胰岛素作用的影响。　方法　在 9只清醒和 9只麻醉的大鼠身上运用正常血糖胰岛素钳夹技术分别进行正常血糖胰岛素钳夹试验 (胰岛素注入率 6 .0mU/ (kg·min)。两组的体重、空腹血糖及胰岛素水平都是相同的。　结果　在胰岛素钳夹过程中 ,两组的血糖及胰岛素浓度都维持于同一水平。在胰岛素钳夹试验的后 6 0～ 90min的稳定期 ,麻醉组大鼠的葡萄糖清除率明显低于清醒大鼠 [14 .3± 0 .7vs2 5 .1± 2 .9mg/ (kg·min) ,P <0 .0 1],葡萄糖代谢率也显示了同样的结果。　结论　麻醉状态影响了正常大鼠的胰岛素感受性。     

氨氯地平对高血压病人胰岛素敏感性的影响

为探讨氨氯地平对高血压病人胰岛素敏感性的干预作用。我们测定２２例高血压病人，２２例正常血压者胰岛素敏感性以及高血压病患者氨氯地平治疗后的胰岛素敏感性变化。以正常血糖胰岛素钳夹技术测定葡萄糖代谢率作为胰鸟敏感性指标。     

大鼠游离脂肪酸的异常蓄积导致骨骼肌胰岛素抵抗机制的研究

目的探讨大鼠骨骼肌游离脂肪酸与胰岛素抵抗（IR）的关系。方法给大鼠静脉输注脂肪乳（多不饱和脂肪酸）＋肝素（NC）及生理盐水7h,并在输注的最后2h,行清醒状态高胰岛素正血糖钳夹试验,测定血浆葡萄糖、胰岛素和C肽水平,观察脂肪酸对胰岛素介导的葡萄糖利用率（GUR）和肝葡萄糖生成（HGP）能力的影响,及脂肪酸在骨骼肌异位沉积的情况。取空腹血测游离脂肪酸（FFA）、甘油三酯（TG）、脂联素等。胰岛素敏感性用正常血糖高胰岛素钳夹技术稳态时的葡萄糖输注率（GIR）来评价。结果与对照组比较,脂肪乳组血浆FFA水平升高（P〈0.01）。在钳夹状态下,脂肪乳组的HGP高于对照组（P〈0.01）,脂肪乳组GUR下降（P〈0.01）。脂肪乳组大鼠的肌肉组织有一定程度的脂肪沉积。结论血浆脂肪酸升高能引起大鼠肌肉组织的IR。     

Comparison of two commonly used insulin injection techniques

In ten patients with insulin-dependent diabetes we compared postprandial blood glucose levels and plasma free insulin concentrations after the administration of insulin mixtures with two commonly used injection techniques. The morning dose of insulin was administered once using a 13 mm needle, inserted perpendicularly, and once with a 20 mm needle, inserted deep subcutaneously just above the muscle fascia at an angle dependent on the skinfold thickness. Plasma free insulin concentrations and postprandial blood glucose levels were virtually identical for either technique. We conclude, therefore, that the simpler perpendicular method is the technique of choice, saving the diabetics much unnecessary anxiety over a daily procedure.     

The short insulin tolerance test for determination of insulin sensitivity: a comparison with the euglycaemic clamp.

The glucose clamp technique is currently regarded as the standard test for measuring insulin sensitivity against which other methods are compared but is unsuitable for routine screening of patients outside a hospital base. There is thus a need for a simpler test to measure insulin sensitivity. We have therefore compared the glucose disappearance rate KITT in the first 15 min of the insulin tolerance test (ITT) with the M and M/I values derived from the standard euglycaemic clamp in nine normal subjects and eight subjects with Type 2 (non-insulin dependent) diabetes mellitus and coexisting obesity. All subjects underwent the ITT and euglycaemic clamp in random order. Nine subjects later had a repeat ITT to determine the reproducibility of the test. In the ITT, 0.1 U kg-1 body weight, human Actrapid insulin was given as an IV bolus and simultaneous arterialized and venous blood samples were obtained every minute for 15 min. The first order rate constant for the disappearance of glucose KITT over the period 3-15 min was taken as a measure of insulin sensitivity. The euglycaemic clamp was performed with an insulin infusion of 50 mU kg-1 h-1 for 120 min and a variable rate glucose infusion to maintain blood glucose concentration at 0.5 mmol l-1 below fasting level to minimize the effect of endogenous insulin secretion. The ratio of the mean rate of glucose infused (M, mumol kg-1 min-1) to the plasma insulin over the last 30 min of the clamp was taken as a measure of tissue sensitivity to insulin (M/I) assuming endogenous glucose output was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

脂质诱导的胰岛素抵抗对大鼠糖代谢的影响

用正糖高胰岛素钳夹术估计脂质灌注大鼠胰岛素介导的外周组织和肝糖代谢。脂质组血浆游离脂肪酸明显升高 ,葡萄糖输注率明显降低 ,胰岛素对肝糖生成的抑制作用明显障碍 ,葡萄糖清除率轻度降低。脂质损害了胰岛素抗脂解和肝糖输出能力及其介导的外周葡萄糖利用     

肥胖对APOE基因型与血浆胰岛素和血糖关系的影响

目的 本文旨在探讨超重／肥胖和载脂蛋白E（APOE）基因型间的交互作用对血浆胰岛素水平和血糖水平的影响。方法 利用北京自然人群横断面研究，应用聚合酶链反应-限制性片段长度多态性技术（PCR—RFLP）进行APOE基因分型，将研究对象以性别、体重指数和基因型分层，比较不同基因型人群血浆胰岛素和血糖水平；分析不同APOE不同基因型和肥胖对血浆胰岛素和血糖水平的影响。结果 （1）随着体重指数的增加，血浆胰岛素和血糖水平明显升高，具有统计学意义；（2）APOE基因型与超重和肥胖的交互作用对血浆胰岛素和血糖水平的影响在女性中具有统计学意义（P=0．003）；（3）与APOE3基因型携带者相比，肥胖的男性APOE2携带者和女性APOFA携带者具有较高的血糖和胰岛素水平。结论 APOE基因多态性对血浆胰岛素和血糖水平的影响受超重／肥胖的调控。     

Effect of the administration of a single dose of nateglinide on insulin secretion at two different concentrations of glucose in healthy individuals

BACKGROUND: Nateglinide is a D-phenylalanine derivative that stimulates fast insulin secretion with a short activity span. It has been suggested that the hypoglycemic effect of nateglinide is related to the glucose concentration, an aspect that still has not been completely evaluated in human beings. OBJECTIVE: The aim of this study is to evaluate the effect of nateglinide on the insulin secretion at two different concentrations of glucose level. PARTICIPANTS AND METHODS: A randomized, double-blind, cross-over, placebo-controlled clinical trial with two parallel groups was carried out; each group was made up by six healthy volunteers who were submitted to a hyperglycemic-hyperinsulinemic clamp technique on two different occasions, one of them prior to the administration of 120 mg nateglinide and the other one prior to the administration of an homologated placebo. One group was submitted to and maintained at a hyperglycemia of 6.9 mmol/l above the fasting glucose level and the other group at a hyperglycemia of 4.1 mmol/l above the baseline of fasting glucose level. RESULTS: In volunteers submitted to the clamp at 4.1 mmol/l above the baseline of glucose level, the insulin secretion in the early phase was 212.4+/-55.8 pmol/l in the placebo test versus 338.4+/-124.8 pmol/l in the nateglinide test (P<.05), whereas in the group submitted at 6.9 mmol/l over the baseline, no significant differences were observed. CONCLUSION: Nateglinide increased the early insulin secretion in healthy individuals submitted to a mild hyperglycemia, but not at high glucose concentrations.     

The action profiles of human NPH insulin preparations

The complete time-action profiles of four subcutaneously injected human NPH insulin preparations (Protaphane HM/Novo; Insulatard Human/Nordisk; Huminsulin Basal/Eli Lilly; Basal H-Insulin/Hoechst) have been investigated by means of the euglycaemic clamp technique (blood glucose 5.0 mmol l-1). Six normal male subjects were connected to a Biostator on five occasions in randomized order including a control study without insulin injection. A stable basal insulin level of about 10 mU l-1 was established by means of a low dose insulin infusion (0.1 mU kg-1 min-1) which subsequently suppressed C-peptide by 35 +/- 19% (mean +/- SD) to levels of around 0.3 nmol l-1. Twelve units of NPH insulin were injected subcutaneously into the abdominal wall and glucose infusion rates were monitored for 19 h. In the control study, the mean glucose infusion rate was 1.11 +/- 0.60 (range 0.32-1.95) mg kg-1 min-1. Maximal glucose infusion rates, reached 5-7 h after injection, were comparable (4.3-4.9 mg kg-1 min-1) for the four different preparations used. Glucose infusion rates returned to basal rates within the 19 h study period. Mean plasma free insulin levels peaked at 17.5-18.6 mU l-1 3-4.5 h after injection and returned to basal levels within 16 h. The time ranges of greater than 90, greater than 75, greater than 50, and greater than 25% of maximal insulin action (as estimated from glucose infusion rates) revealed no significant differences between the four insulin preparations tested. No significant insulin action was observed beyond 17 h after insulin injection of any preparation.     

家族性高血压病患者的胰岛素抗性及其受体变化

我们通过对15例家族性高血压病患者和10例年龄、性别、体重指数相当的正常对照者的比较发现,两者的空腹血糖和血清胰岛素水平相当,均正常;但家族性高血压病患者血糖和胰岛素的反应曲线下面积显著性高于正常对照组,且恢复时间显著延长。这证明:家族性高血压病患者存在糖耐量异常和胰岛素抗性,并且家族性高血压病患者的红细胞胰岛素受体数目减少。进一步分析发现,其特异性胰岛素结合率与基础的血糖和胰岛素水平,以及服糖180分钟内血糖反应曲线下面积无关,但与服糖后180分钟内胰岛素反应曲线下面积呈负相关。这提示,家族性高血压病患者红细胞胰岛素受体缺陷,可加重胰岛素抗性,但不是产生糖耐量减低和胰岛素抗性的主要原因。     

Understanding Oral Glucose Tolerance: Comparison of Glucose or Insulin Measurements During the Oral Glucose Tolerance Test with Specific Measurements of Insulin Resistance and Insulin Secretion

The extent to which the oral glucose tolerance test can be used to estimate insulin secretion and insulin resistance has been evaluated by comparing glucose and insulin concentrations during an oral glucose tolerance test with specific measurements of insulin secretion and insulin resistance in 85 normoglycaemic subjects and 23 subjects with impaired glucose tolerance (IGT). Insulin secretion was measured by the first phase insulin response to intravenous glucose and insulin resistance by the insulin tolerance test which measures the decline of plasma glucose after the injection of a bolus of insulin. The best measure of insulin secretion was the ratio of the 30 min increment in insulin concentration to the 30 min increment in glucose concentration following oral glucose loading. This correlated with the first phase insulin release following intravenous glucose (r=0.61, p < 0.001) but not insulin resistance (r= ?0.05, p >0.05). Insulin resistance could be estimated by the fasting insulin, proinsulin, or split proinsulin concentrations. However, fasting split proinsulin appeared to discriminate best between insulin resistance (r = ?0.53, p < 0.001) and insulin secretion (r = 0.07, p > 0.05). Relative insulin resistance estimated by homeostasis model assessment (HOMA) also correlated well with insulin resistance (r= ?0.57, p < 0.001) but not insulin secretion (r= 0.01, p > 0.05). We conclude that the oral glucose tolerance test can be used to derive estimates of the relative roles of insulin secretion and insulin resistance in population studies of glucose tolerance.     

高血压患者血糖及血胰岛素水平的观察

对６９例高血压患者进行口服葡萄糖耐量试验、胰岛素和Ｃ肽释放试验，并与５５例血压正常者作比较。结果示高血压组空腹及服糖后各时相的血糖水平和糖代谢失常（ＤＭ＋ＩＧＴ）发生率、血清胰岛素水平及Ｃ肽水平都高于血压正常对照组。高血压患者血胰岛素水平增高而血糖水平未见相应降低，提示胰岛素抵抗的存在。