Iwase Masanori, Nakamura Udai, Uchizono Yuji, Nohara Sakae, Sasaki Nobuhiro, Sonoki Kazuo, Iida Mitsuo
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
Eur J Pharmacol. 2005 Aug 22;518(2-3):243-50. doi: 10.1016/j.ejphar.2005.05.044.
We studied whether the rapid hypoglycemic action of nateglinide is associated with an increase in islet blood flow. Islet blood flow was measured using the two-colour microsphere method. Orally administered nateglinide with glucose acutely increased islet blood flow to levels greater than those after glucose alone or tolbutamide with glucose in conscious Sprague-Dawley rats (percent increase at 10 min after oral administration; nateglinide+glucose, 125+/-25%; glucose, 33+/-11%, p<0.001; tolbutamide+glucose, 42+/-23%, p<0.01). Nateglinide administered with non-metabolisable 3-O-methylglucose also increased islet blood flow (61+/-17%). The stimulated islet blood flow significantly correlated with serum insulin levels. N(G)-monomethyl-L-arginine, a nitric oxide synthase inhibitor, completely inhibited the increase in islet blood flow induced by nateglinide with glucose. Intravenously administered nateglinide did not significantly affect the already increased islet blood flow in diabetic Otsuka Long-Evans Tokushima Fatty rats. Our results indicated that nateglinide acutely increased islet blood flow at least in part through a nitric oxide-dependent mechanism.
我们研究了那格列奈的快速降糖作用是否与胰岛血流增加有关。采用双色微球法测量胰岛血流。在清醒的斯普拉格-道利大鼠中，口服那格列奈与葡萄糖可使胰岛血流急性增加至高于单独给予葡萄糖或甲苯磺丁脲与葡萄糖后的水平（口服给药后10分钟的增加百分比；那格列奈+葡萄糖，125±25%；葡萄糖，33±11%，p<0.001；甲苯磺丁脲+葡萄糖，42±23%，p<0.01）。那格列奈与不可代谢的3-O-甲基葡萄糖一起给药也可增加胰岛血流（61±17%）。刺激后的胰岛血流与血清胰岛素水平显著相关。一氧化氮合酶抑制剂N(G)-单甲基-L-精氨酸完全抑制了那格列奈与葡萄糖诱导的胰岛血流增加。静脉注射那格列奈对糖尿病大冢长-艾氏-德岛肥胖大鼠中已经增加的胰岛血流没有显著影响。我们的结果表明，那格列奈至少部分通过一氧化氮依赖性机制急性增加胰岛血流。
