Iwakura Hiroshi, Hosoda Kiminori, Son Choel, Fujikura Junji, Tomita Tsutomu, Noguchi Michio, Ariyasu Hiroyuki, Takaya Kazuhiko, Masuzaki Hiroaki, Ogawa Yoshihiro, Hayashi Tatsuya, Inoue Gen, Akamizu Takashi, Hosoda Hiroshi, Kojima Masayasu, Itoh Hiroshi, Toyokuni Shinya, Kangawa Kenji, Nakao Kazuwa
Department of Medicine and Clinical Science, Endocrinology and Metabolism, Kyoto University Graduate School of Medicine, Japan.
J Biol Chem. 2005 Apr 15;280(15):15247-56. doi: 10.1074/jbc.M411358200. Epub 2005 Feb 8.
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 radioimmunoassay (RIA) and plasma desacyl ghrelin concentration of RIP-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.
大鼠胰岛素II启动子-胃饥饿素转基因小鼠（RIP-G Tg）和大鼠胰高血糖素启动子-胃饥饿素转基因小鼠（RGP-G Tg）。通过C端放射免疫分析法（RIA）测得的RIP-G Tg胰腺组织胃饥饿素浓度以及血浆去酰基胃饥饿素浓度分别比非转基因同窝小鼠高约1000倍和3.4倍。通过N端RIA测得的RIP-G Tg胰腺组织正辛酰化胃饥饿素浓度以及血浆正辛酰化胃饥饿素浓度与非转基因同窝小鼠无显著差异。RIP-G Tg表现出葡萄糖刺激的胰岛素分泌受到抑制。RIP-G Tg胰腺中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、胰岛结构以及GLUT2和PDX-1免疫反应性与非转基因同窝小鼠无显著差异。胰岛批量孵育研究未显示RIP-G Tg在体外胰岛素分泌受到抑制。胰岛素耐量试验显示RIP-G Tg的血糖水平有降低趋势。考虑到RIP-G Tg甘油三酯水平也有降低趋势，这些结果可能表明胰岛素分泌受到抑制可能是由于去酰基胃饥饿素对胰岛素敏感性的影响。RGP-G Tg通过C-RIA测得的胰腺组织胃饥饿素浓度比非转基因同窝小鼠高约50倍，其胰岛素分泌、葡萄糖代谢、胰岛质量和胰岛结构均无显著变化。本研究提出了去酰基胃饥饿素可能对葡萄糖代谢有影响的可能性。
