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Platelet resistance to nitrates in obesity and obese NIDDM, and normal platelet sensitivity to both insulin and nitrates in lean NIDDM.
肥胖和肥胖 NIDDM 中的血小板对硝酸盐的抵抗,以及瘦 NIDDM 中的正常血小板对胰岛素和硝酸盐的敏感性。

摘要

OBJECTIVE:Previous studies in our laboratory showed that the platelet anti-aggregating effect exerted by insulin, mediated by a nitric oxide (NO)-induced increase of guanosine-3',5'-cyclic monophosphate (cGMP), is lost in the insulin-resistant of obesity and obese NIDDM. It is not clear 1) whether the alterations observed in obese NIDDM patients are attributable to the obesity-related insulin resistance or to diabetes per se and 2) whether insulin-resistant states present a normal or a blunted response to NO. This study has been conducted to investigate 1) the platelet sensitivity to insulin in lean NIDDM and 2) the platelet sensitivity to an NO donor, glyceryl trinitrate (GTN), in obesity and in both lean and obese NIDDM.
RESEARCH DESIGN AND METHODS:We determined 1) ADP-induced platelet aggregation and platelet cGMP content in platelet-rich plasma (PRP) obtained from 11 lean NIDDM patients, after a 3-min incubation with insulin (0, 240, 480, 960, 1,920 pmol/l) and 2) ADP-induced platelet aggregation and platelet cGMP content in PRP obtained from 9 obese subjects, 11 lean and 8 obese NIDDM patients, and 18 control subjects, after a 3-min incubation with 0, 20, 40, and 100 mumol/l GTN.
RESULTS:Insulin dose-dependently decreased platelet aggregation in lean NIDDM patients (P = 0.0001): with 1,920 pmol/l of insulin, ADP ED50 was 141.5 +/- 6.4% of basal values (P = 0.0001). Furthermore, insulin increased platelet cGMP (P = 0.0001) from 7.5 +/- 0.2 to 21.1 +/- 3.7 pmol/10(9) platelets. These results were similar to those previously described in healthy subjects. GTN reduced platelet aggregation in all the groups (P = 0.0001) at all the concentrations tested (P = 0.0001), but GTN IC50 values were much higher in insulin-resistant patients: 36.3 +/- 5.0 mumol/l in healthy control subjects, 26.0 +/- 6.0 mumol/l in lean NIDDM patients (NS vs. control subjects), 123.6 +/- 24.0 mumol/l in obese subjects (P = 0.0001 vs. control subjects), and 110.1 +/- 19.2 mumol/l in obese NIDDM patients (P = 0.0001 vs. control subjects). GTN dose-dependently increased platelet cGMP in all the groups (P = 0.0001 in control subjects, lean NIDDM patients, and obese subjects; P = 0.04 in obese NIDDM patients). Values reached by obese subjects and obese NIDDM patients, however, were lower than those reached by control subjects (with 100 mumol/l of GTN, P = 0.001 and P = 0.0001, respectively). In healthy control subjects and in obese subjects, the insulin:glucose ratio, used as an indirect measure of insulin sensitivity, was positively correlated to GTN IC50 (r = 0.530, P = 0.008), further suggesting that the sensitivity to NO is reduced in the presence of insulin resistance.
CONCLUSIONS:The insulin anti-aggregating effect is preserved in lean NIDDM; platelet sensitivity to GTN in preserved in lean NIDDM but is reduced in the insulin-resistant states of obesity and obese NIDDM. Resistance to nitrates, therefore, could be considered another feature of the insulin-resistance syndrome.

译文

目的: 我们实验室先前的研究表明,胰岛素发挥的血小板抗聚集作用,是由一氧化氮 (NO) 诱导的 guanosine-3 增加所介导的, 5 '-环磷酸腺苷 (cGMP),在肥胖和肥胖 NIDDM 的胰岛素抵抗中丢失。尚不清楚 1) 在肥胖 NIDDM 患者中观察到的改变是归因于肥胖相关的胰岛素抵抗还是糖尿病本身,2) 胰岛素抵抗状态对 NO 的反应是正常的还是迟钝的本研究旨在研究 1) 精益 NIDDM 中血小板对胰岛素的敏感性和 2) 血小板对无供体三色甘油酯 (GTN) 的敏感性, 在肥胖者以及瘦和肥胖者中。
研究设计和方法: 我们测定了 1) 从 11 名瘦 NIDDM 患者获得的富血小板血浆 (PRP) 中 ADP 诱导的血小板聚集和血小板 cGMP 含量, 用胰岛素 (0 、 240 、 480 、 960 、 1,920 pmol/l) 和 2) 孵育 3 分钟后ADP 诱导的 PRP 中血小板聚集和血小板 cGMP 含量来自 9 名肥胖受试者、 11 名瘦肉和 8 名肥胖 NIDDM 患者以及 18 名对照组,在与 0 、 20 、 40 和 100 mumol/l GTN。
结果: 胰岛素剂量依赖性地减少瘦 NIDDM 患者的血小板聚集 (P = 0.0001): 胰岛素浓度为 1,920 pmol/l, ADP ED50 为基础值的 141.5/-6.4% (P = 0.0001)。此外,胰岛素使血小板 cGMP (P = 0.0001) 从 7.5/-0.2 增加到 21.1/-3.7 pmol/10 (9) 血小板。这些结果与之前描述的健康受试者的结果相似。GTN 降低了所有测试浓度组 (P = 0.0001) 的血小板聚集 (P = 0.0001),但是在胰岛素抵抗患者中 GTN IC50 值要高得多: 健康对照组 36.3/-5.0 mumol/l,瘦 NIDDM 患者 26.0/-6.0 mumol/l (NS vs.对照组),肥胖受试者 123.6/-24.0 mumol/l (P = 0.0001 vs.对照组),肥胖 NIDDM 患者 110.1/-19.2 mumol/l (P = 0.0001 vs.对照组)。GTN 剂量依赖性增加了所有组的血小板 cGMP (对照组、瘦 NIDDM 患者和肥胖受试者 P = 0.0001; 肥胖 NIDDM 患者 P = 0.04)。然而,肥胖受试者和肥胖 NIDDM 患者达到的值低于对照组 (GTN 为 100 mumol/l,P = 0.001 和 P = 0.0001)。在健康对照组和肥胖受试者中,胰岛素与葡萄糖的比值,作为胰岛素敏感性的间接测量,与 GTN IC50 呈正相关 (r = 0.530,P = 0.008), 进一步提示在胰岛素抵抗的存在下,对 NO 的敏感性降低。
结论: 胰岛素抗聚集作用在瘦肉型 NIDDM 中得以保留; 血小板对 GTN 的敏感性在瘦肉型 NIDDM 中得以保留,但在肥胖和肥胖 NIDDM 的胰岛素抵抗状态下得以降低。因此,对硝酸盐的抗性可以被认为是胰岛素抵抗综合征的另一个特征。

Platelet resistance

心血管 动脉粥样硬化 临床研究术语
概述  :  

血小板的活化及血栓形成是动脉粥样硬化及其相关心脑血管事件的重要病理基础,因此,抗血小板抗栓治疗成为防治这类疾病必不可少的重要环节。大量证据表明,阿司匹林作为抗血小板抗栓药是心脑血管事件一级预防和二级预防的基石:尽管如此,由于接受阿司匹林治疗的患者再发血管性事件的风险仍相对较高(2年8%-18%),从而提出“阿司匹林抵抗”的概念。目前对阿司匹林抵抗的主要药物防治措施是联合氯吡格雷治疗,但又出现了“氯吡格雷抵抗”现象,提示有效的抗血小板治疗远比最初所认识的复杂和困难。因此,我们提出,在一种或多种

Platelet 英 ['pleɪtlɪt] 美 ['pletlət]

释义   n.  [组织] 血小板;薄片

例句   It is simply a matter of decreasing sequestration and destruction of platelet.

这只是一个减少血小板的隔离与破坏的问题。

 

Resistance 英 [rɪ'zɪst(ə)ns] 美 [rɪ'zɪstəns]

释义   n. 阻力;电阻;抵抗;反抗;抵抗力

例句   You have the ability to look here where there is not resistance.

你有能力在没有阻力的地方观察。


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