Tacrolimus-induced diabetes in rats courses with suppressed insulin gene expression in pancreatic islets
Tacrolimus-induced diabetes in rats courses with suppressed insulin gene expression in pancreatic islets
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DOI：
10.1111/j.1600-6143.2007.01946.x
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发表时间：
2007-11-01
影响因子：
8.8
通讯作者：
Tamarit-Rodriguez, J.
中科院分区：
文献类型：
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作者：
Hernandez-Fisac, I.;Pizarro-Delgado, J.;Tamarit-Rodriguez, J.
通过每天以0.1 mg/kg体重的他克莫司（FK 506）分两次腹腔注射给药，在大鼠中诱导移植后糖尿病动物模型。治疗9天后，大鼠出现高血糖症和葡萄糖耐受不良。胰岛，从处理大鼠在不同的日子，分离，显示出降低的能力，分泌胰岛素的20 mM葡萄糖在第7天和第14天。在这种胰岛素分泌抑制之前，在第5天胰岛胰岛素含量降低，其逐渐降低直至治疗结束（第14天）。在第7天和第14天，从大鼠胰岛素基因1和2转录的胰岛素mRNA的胰岛含量被强烈抑制，类似于胰岛素含量。他克莫司处理对胰岛质量没有显著影响：DNA含量在最后（第14天）略有下降，胰岛细胞凋亡率略有增加。他克莫司诱导的大鼠糖尿病似乎主要是由胰岛素基因转录减少引起的，而胰岛质量几乎没有改变。这解释了在中断他克莫司治疗后2周，观察到的所有研究的胰岛和动物参数的抑制完全逆转。
An animal model of post-transplant diabetes was induced in rats by treating them daily with 0.1 mg/kg body weight of tacrolimus (FK506) in two i.p. injections. Rats developed hyperglycaemia and glucose intolerance after 9 days of treatment. Pancreatic islets, isolated from treated rats on different days, showed a decreased capacity to secrete insulin in response to 20 mM glucose at days 7 and 14. This suppression of insulin secretion was preceded by a reduction of the islet insulin content on day 5 that was progressively decreasing until the end of the treatment (day 14). Islet content of insulin mRNAs, transcribed from rat insulin genes 1 and 2, was strongly suppressed, similar to the insulin content, at days 7 and 14. Islet mass was not strikingly modified by tacrolimus treatment: the DNA content was slightly decreased at the end (day 14) and the rate of islet cell apoptosis slightly increased. Tacrolimus-induced diabetes in the rat seems to be mainly provoked by a decreased insulin gene transcription with little or no alteration of islet mass. This explains that the observed suppression of all the islet and animal parameters studied was completely reversed 2 weeks after interrupting tacrolimus treatment.