Acute and long-term effects of nateglinide on insulin secretory pathways
Acute and long-term effects of nateglinide on insulin secretory pathways
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DOI：
10.1038/sj.bjp.0705766
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发表时间：
2004-05-01
影响因子：
7.3
通讯作者：
McClenaghan, NH
中科院分区：
文献类型：
--
作者：
Ball, AJ;Flatt, PR;McClenaghan, NH
1在BRIM-BD 11细胞系中检测促胰岛素药物那格列奈对胰岛素释放的急性和慢性作用。2在非刺激性（1.1 mM）葡萄糖浓度下，那格列奈（10-400 μ M）刺激胰岛素释放的浓度依赖性增加（P < 0.05-P < 0.001）。对200 μ M那格列奈的促胰岛素反应在30 mM时增加，（P < 0.01），但不是5.6-16.7 mM葡萄糖浓度。3在去极化细胞中，nateglinide（50-200 μ M）诱发K-ATP通道非依赖性胰岛素分泌在不存在和存在5.6-30.0 mM葡萄糖的情况下（P < 0.05-P < 0.001）（P < 0.001）。4暴露于100 μ M那格列奈18小时可消除200 μ M那格列奈、甲苯磺丁脲或格列本脲的急性促胰岛素作用，但对200 μ M依法克生的促胰岛素作用没有影响。5虽然暴露于100 μ M那格列奈18小时不影响基础胰岛素释放或在16.7 mM葡萄糖、25 μ M毛喉素或10 nM PMA存在下的胰岛素释放，20目的亮氨酸和目的精氨酸的促胰岛素作用的显著抑制被证实。6这些数据表明那格列奈刺激K-ATP通道依赖性和非依赖性胰岛素分泌。随着葡萄糖浓度的增加，该药物维持促胰岛素作用，支持那格列奈在II型糖尿病中的抗高血压作用。7那格列奈长期作用的研究表明，那格列奈与磺脲类药物共享信号通路，但与咪唑啉依伐克生不同。当考虑那格列奈治疗方案时，这可能是重要的，特别是在既往接受过磺脲类药物治疗的患者中。
1 Acute and chronic effects of the insulinotropic drug nateglinide upon insulin release were examined in the BRIM-BD11 cell line.2 Nateglinide (10-400 muM) stimulated a concentration-dependent increase (P < 0.05-P < 0.001) in insulin release at a non-stimulatory (1.1 mM) glucose concentration. The insulinotropic response to 200 muM nateglinide was increased at 30 mM (P < 0.01), but not 5.6-16.7 mM glucose concentrations.3 In depolarized cells, nateglinide (50-200 mu M) evoked K-ATP channel-independent insulin secretion (P < 0.05-P < 0.001) in the absence and presence of 5.6-30.0 mM glucose (P < 0.001).4 Exposure for 18h to 100 muM nateglinide abolished the acute insulinotropic effects of 200 muM nateglinide, tolbutamide or glibenclamide, but had no effect upon the insulinotropic effect of 200 muM efaroxan.5 While 18h exposure to 100 muM nateglinide did not affect basal insulin release or insulin release in the presence of 16.7 mM glucose, 25 muM forskolin or 10 nM PMA, significant inhibition of the insulinotropic effects of 20 aim leucine and Maim arginine were observed.6 These data show that nateglinide stimulates both K-ATP channel-dependent and-independent insulin secretion. The maintained insulinotropic effects of this drug with increasing glucose concentrations support the antihyperglycaemic actions of nateglinide in Type II diabetes.7 Studies of the long-term effects of nateglinide indicate that nateglinide shares signalling pathways with sulphonylureas, but not the imidazoline efaroxan. This may be significant when considering a nateglinide treatment regimen, particularly in patients previously treated with sulphonylurea.