Malaisse Willy J, Lebrun Philippe, Sener Abdullah, Wolters Gerrit H J, Ravazzola Mariella
Laboratories of Experimental Hormonology and Pharmacology, Brussels Free University, Brussels, Belgium.
Endocrine. 2004 Jun;24(1):83-91. doi: 10.1385/ENDO:24:1:083.
Thioacetamide (0.01-1.3 mM) fails to exert any significant immediate effect upon insulin release from rat isolated islets. However, when administered (4 micromol/g body wt) intraperitoneally 24 h before sacrifice, it reduced food intake and body weight and affected the secretory response of isolated islets to several secretagogues, despite unaltered insulin content of such islets. This coincided with a decrease in D-[U-14C]glucose oxidation, total islet calcium content and the ionized calcium content of secretory granules in islet B-cells, and changes in both 133Ba and 45Ca net uptake. Likewise, in islets prepared from thioacetamide-injected rats and prelabeled with 45Ca before perifusion, the cationic and insulin secretory responses to D-glucose or gliclazide, but not to the association of Ba2+ and theophylline in the absence of extracellular Ca2+, often differed from that otherwise found in islets prepared from control rats. These findings are interpreted as indicative of an impaired capacity of Ca2+ sequestration by intracellular organelles in the islet B-cells of thioacetamide-treated rats.
硫代乙酰胺(0.01 - 1.3 mM)对从大鼠分离出的胰岛释放胰岛素没有任何显著的即时作用。然而,在处死前24小时腹腔注射(4微摩尔/克体重)时,它减少了食物摄入量和体重,并影响了分离出的胰岛对几种促分泌剂的分泌反应,尽管这些胰岛的胰岛素含量未改变。这与D - [U - 14C]葡萄糖氧化、胰岛总钙含量以及胰岛B细胞分泌颗粒的离子钙含量的降低,以及133Ba和45Ca净摄取的变化同时发生。同样,在从注射硫代乙酰胺的大鼠制备并在灌流前用45Ca预标记的胰岛中,对D - 葡萄糖或格列齐特的阳离子和胰岛素分泌反应,但在没有细胞外Ca2 +的情况下对Ba2 +和茶碱的联合反应,通常与从对照大鼠制备的胰岛中发现的情况不同。这些发现被解释为表明硫代乙酰胺处理的大鼠胰岛B细胞中细胞内细胞器对Ca2 +的螯合能力受损。