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首页> 外文期刊>American Journal of Physiology >A mouse model of ghrelinoma exhibited activated growth hormone-insulin-like growth factor I axis and glucose intolerance.
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A mouse model of ghrelinoma exhibited activated growth hormone-insulin-like growth factor I axis and glucose intolerance.

机译：生长激素释放瘤的小鼠模型表现出活化的生长激素-胰岛素样生长因子I轴和葡萄糖耐量。

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Ghrelin is a stomach-derived peptide that has growth hormone-stimulating and orexigenic activities. Although there have been several reports of ghrelinoma cases, only a few cases have elevated circulating ghrelin levels, hampering the investigation of pathophysiological features of ghrelinoma and chronic effects of ghrelin excess. Furthermore, standard transgenic technique has resulted in desacyl ghrelin production only because of the limited tissue expression of ghrelin O-acyltransferase, which mediates acylation of ghrelin. Accordingly, we attempted to create ghrelin promoter SV40 T-antigen transgenic (GP-Tag Tg) mice, in which ghrelin-producing cells continued to proliferate and finally developed into ghrelinoma. Adult GP-Tag Tg mice showed elevated plasma ghrelin levels with preserved physiological regulation. Adult GP-Tag Tg mice with increased plasma ghrelin levels exhibited elevated IGF-I levels despite poor nutrition. Although basal growth hormone levels were not changed, those after growth hormone-releasing hormone injection tended to be higher. These results indicate that chronic elevation of ghrelin activates GH-IGF-I axis. In addition, GP-Tag Tg mice demonstrated glucose intolerance. Insulin secretion by glucose tolerance tests was significantly attenuated in GP-Tag Tg, whereas insulin sensitivity determined by insulin tolerance tests was preserved, indicating that chronic elevation of ghrelin suppresses insulin secretion and leads to glucose intorelance. Thus, we successfully generated a Tg model of ghrelinoma, which is a good tool to investigate chronic effects of ghrelin excess. Moreover, their characteristic features could be a hint on ghrelinoma.
机译：Ghrelin是一种胃衍生肽，具有刺激生长激素和致癌活性。尽管有几例关于生长激素释放瘤的报道，但只有少数病例的生长激素释放肽水平升高，这阻碍了对生长激素释放瘤的病理生理特征和生长激素释放肽过量的慢性影响的研究。此外，仅由于生长素释放肽O-酰基转移酶在组织中的表达有限而介导生长素释放肽的酰化，所以标准的转基因技术仅产生了脱酰基生长素释放肽。因此，我们尝试创建生长素释放肽启动子SV40 T-抗原转基因（GP-Tag Tg）小鼠，其中产生生长素释放肽的细胞持续增殖并最终发展为生长激素释放瘤。成年GP-Tag Tg小鼠显示血浆生长素释放肽水平升高，且生理调节保持不变。尽管营养不良，但血浆生长素释放肽水平升高的成年GP-Tag Tg小鼠仍表现出较高的IGF-I水平。尽管基础生长激素水平没有改变，但注射生长激素释放激素后的基础水平趋于更高。这些结果表明生长素释放肽的慢性升高激活了GH-IGF-1轴。另外，GP-Tag Tg小鼠表现出葡萄糖耐受不良。在GP-Tag Tg中，葡萄糖耐量试验的胰岛素分泌显着减弱，而胰岛素耐量试验确定的胰岛素敏感性得以保留，这表明生长激素释放肽的长期升高会抑制胰岛素分泌并导致葡萄糖摄入不足。因此，我们成功地生成了ghrelinoma的Tg模型，这是研究ghrelin过量的慢性影响的良好工具。此外，它们的特征可能暗示了生长激素释放瘤。

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