Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus.
Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus.
复制标题
尾加压素-II 受体拮抗剂帕洛苏兰对 2 型糖尿病患者胰岛素分泌和敏感性的影响。
DOI：
10.1111/j.1365-2125.2009.03480.x
复制
发表时间：
2009
影响因子：
3.4
通讯作者：
J. Dingemanse
中科院分区：
文献类型：
--
作者：
P. Sidharta;K. Rave;L. Heinemann;E. Chiossi;S. Krähenbühl;J. Dingemanse
目标
目的：在一项双盲、安慰剂对照、随机、交叉、概念验证的研究中，研究尾加压素-II受体的非肽类、有效和选择性拮抗剂帕罗舒兰对20例饮食治疗的2型糖尿病患者胰岛素和血糖调节的影响。
方法
服药4周后，通过高血糖钳夹试验、餐耐量试验、稳态模型评估-胰岛素抵抗评分和每日自我血糖监测来评估对胰岛素分泌、胰岛素敏感性和血糖水平的影响。在服药的最后一天测定12小时内的血药浓度。
结果
与安慰剂相比，Palosuran对高血糖葡萄糖钳夹期间的第二时相胰岛素反应(主要终点)没有影响[配对差异-1.8微U ml(-1)，95%可信区间(CI)-7.8，4.2]。同样，在饮食耐量试验期间，没有检测到Palosuran对第一时相胰岛素反应、对胰岛素分泌和血糖水平、对稳态模型评估-胰岛素抵抗评分的影响。在研究期间，没有观察到对每日血糖谱有显著临床意义的影响。几何平均值C(Max)和AUC(Tau)(95%CI)和中位数t(Max)(范围)分别为180ng.hml(-1)(125,260)、581ng.hml(-1)(422,800)和3.0h(0.67，4.3)。
结论
这项研究的结果表明，尾加压素-II系统的拮抗不会影响2型糖尿病饮食治疗患者的胰岛素分泌或敏感性或每日血糖水平。
AIMS
To investigate the effects of palosuran, a nonpeptidic, potent and selective antagonist of the urotensin-II receptor, on insulin and glucose regulation in 20 diet-treated patients with Type 2 diabetes mellitus in a double-blind, placebo-controlled, randomized, crossover, proof-of-concept study.
METHODS
After 4 weeks' oral treatment with 125 mg palosuran or placebo b.i.d.,effects on insulin secretion and sensitivity and blood glucose levels were assessed by means of a hyperglycaemic glucose clamp, meal tolerance test, homeostasis model assessment-insulin resistance score, and daily self-monitoring of blood glucose. Plasma concentrations of palosuran were determined for 12 h on the last day of intake.
RESULTS
Palosuran did not affect second-phase insulin response (primary end-point) during the hyperglycaemic glucose clamp in comparison with placebo [paired difference of -1.8 microU ml(-1), 95% confidence interval (CI) -7.8, 4.2]. Likewise, no effects of palosuran were detected on the first-phase insulin response, or on insulin secretion and blood glucose levels during the meal tolerance test or on homeostasis model assessment-insulin resistance score. No clinically significant effects on daily blood glucose profiles were observed during the study. Geometric mean C(max) and AUC(tau) (95% CI) and median t(max) (range) in this patient population were 180 ng ml(-1) (125, 260), 581 ng.h ml(-1) (422, 800) and 3.0 h (0.67, 4.3), respectively.
CONCLUSIONS
The results of this study indicate that antagonism of the urotensin-II system does not influence insulin secretion or sensitivity or daily blood glucose levels in diet-treated patients with Type 2 diabetes.
影响因子：
3
作者：
Totsune, K;Takahashi, K;Imai, Y
通讯作者：
Imai, Y
日本人尾加压素 II 和尾加压素 II 受体基因的遗传变异与 2 型糖尿病风险
影响因子：
3
作者：
Susumu Suzuki;Z. Wenyi;M. Hirai;Y. Hinokio;Chitose Suzuki;Takahiro Yamada;Shinsuke Yoshizumi;Michiko Suzuki;Y. Tanizawa;A. Matsutani;Y. Oka
通讯作者：
Y. Oka