title: Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagon promoter-ghrelin transgenic mice.
abstract: 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.
authors.affiliation: Department of Medicine and Clinical Science, Endocrinology and Metabolism, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwakura
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Choel
authors.initials: C
authors.lastname: Son
authors.forename: Junji
authors.initials: J
authors.lastname: Fujikura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tomita
authors.forename: Michio
authors.initials: M
authors.lastname: Noguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ariyasu
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takaya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Gen
authors.initials: G
authors.lastname: Inoue
authors.forename: Takashi
authors.initials: T
authors.lastname: Akamizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kojima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D015152:Blotting, Northern; D001835:Body Weight; D018076:DNA, Complementary / Q000378:metabolism; D015723:Gene Library; D054439:Ghrelin; D005934:Glucagon / Q000235:genetics*; D005947:Glucose / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D000078790:Insulin Secretion; D007438:Introns; D007515:Islets of Langerhans / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D010179:Pancreas / Q000378:metabolism; D036361:Peptide Hormones / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D054439:Ghrelin; D018398:Homeodomain Proteins; D007328:Insulin; D036361:Peptide Hormones; D010455:Peptides; D012333:RNA, Messenger; D015534:Trans-Activators; C422650:ghrelin, des-n-octanoyl; C084010:pancreatic and duodenal homeobox 1 protein; D005934:Glucagon; D001120:Arginine; D005947:Glucose