Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagon promoter-ghrelin transgenic mice
Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagon promoter-ghrelin transgenic mice
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DOI：
10.1074/jbc.m411358200
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发表时间：
2005-04-15
影响因子：
4.8
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Iwakura, H;Hosoda, K;Nakao, K
我们开发并分析了两种类型的转基因小鼠：大鼠胰岛素II启动子-ghrelin转基因小鼠（RIP-G Tg）和大鼠胰高血糖素启动子-ghrelin转基因小鼠（RGP-G Tg）。用C-末端放射免疫测定法（RIA）测定的胰腺组织ghrelin浓度和血浆去酰基ghrelin浓度分别是非转基因同窝仔的1000倍和3.4倍。通过N-末端RIA测量的胰腺组织n-辛酰化生长素释放肽浓度和RIP-G Tg的血浆n-辛酰化生长素释放肽浓度与非转基因同窝仔的那些没有区别。RIP-G Tg显示抑制葡萄糖刺激的胰岛素分泌。精氨酸刺激的胰岛素分泌，胰腺胰岛素mRNA和肽水平，β细胞质量，胰岛结构，GLUT 2和PDX-1免疫反应性在RIP-G Tg胰腺与非转基因同窝仔没有显着差异。胰岛分批孵育研究未显示RIP-G Tg在体外抑制胰岛素分泌。胰岛素耐量试验显示RIP-G Tg组血糖水平有降低趋势。考虑到RIP-G Tg的甘油三酯水平较低的趋势，这些结果可能表明胰岛素分泌的抑制可能是由于去酰基ghrelin对胰岛素敏感性的影响。RGP-G Tg，其中通过C-RIA测量的胰腺组织ghrelin浓度比非转基因同窝仔高约50倍，在胰岛素分泌、葡萄糖代谢、胰岛质量和胰岛结构方面没有显示出显著变化。本研究提出了去酰基ghrelin可能影响葡萄糖代谢的可能性。
We developed and analyzed two types of transgenic mice: rat insulin II promoter-ghrelin transgenic (RIP-G Tg) and rat glucagon promoter-ghrelin transgenic mice (RGP-G Tg). The pancreatic tissue ghrelin concentration measured by C-terminal radioimmuno-assay (RIA) and plasma desacyl ghrelin concentration ofRIP-G Tg were about 1000 and 3.4 times higher than those of nontransgenic littermates, respectively. The pancreatic tissue n-octanoylated ghrelin concentration measured by N-terminal RIA and plasma n-octanoylated ghrelin concentration of RIP-G Tg were not distinguishable from those of nontransgenic littermates. RIP-G Tg showed suppression of glucose-stimulated insulin secretion. Arginine-stimulated insulin secretion, pancreatic insulin mRNA and peptide levels, beta cell mass, islet architecture, and GLUT2 and PDX-1 immunoreactivity in RIP-G Tg pancreas were not significantly different from those of nontransgenic littermates. Islet batch incubation study did not show suppression of insulin secretion of RIP-G Tg in vitro. The insulin tolerance test showed lower tendency of blood glucose levels in RIP-G Tg. Taking lower tendency of triglyceride level of RIP-G Tg into consideration, these results may indicate that the suppression of insulin secretion is likely due to the effect of desacyl ghrelin on insulin sensitivity. RGP-G Tg, in which the pancreatic tissue ghrelin concentration measured by C-RIA was about 50 times higher than that of nontransgenic littermates, showed no significant changes in insulin secretion, glucose metabolism, islet mass, and islet architecture. The present study raises the possibility that desacyl ghrelin may have influence on glucose metabolism.