Krogsgaard Thomsen M, Bokvist K, Høy M, Buschard K, Holst J J, Lindström P, Gromada J
Novo Nordisk, Bagsvaerd, Denmark.
Diabetes Nutr Metab. 2002 Dec;15(6 Suppl):15-8.
To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in rat pancreatic alpha-cells and somatotrophs. We found a pharmacological dissociation between the actions on KATP channels and exocytosis and suggest that compounds that, unlike repaglinide, have direct stimulatory effects on exocytosis in somatotrophs and alpha- and beta-cells, such as sulphonylureas and nateglinide, may have a clinically undesirable general stimulatory effect on cells within the endocrine system.
为了研究餐时血糖调节剂的激素和细胞选择性,我们进行了一系列实验,在这些实验中,我们表征了瑞格列奈和那格列奈对大鼠胰腺α细胞和生长激素细胞中ATP敏感性钾离子(KATP)通道活性、膜电位和胞吐作用的影响。我们发现了KATP通道作用与胞吐作用之间的药理学解离,并表明与瑞格列奈不同,对生长激素细胞以及α细胞和β细胞中的胞吐作用有直接刺激作用的化合物,如磺脲类药物和那格列奈,可能对内分泌系统内的细胞产生临床上不良的普遍刺激作用。