Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagon promoter-ghrelin transgenic mice.
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.
Iwakura
Hiroshi
H
Department of Medicine and Clinical Science, Endocrinology and Metabolism, Kyoto University Graduate School of Medicine, Japan.
Hosoda
Kiminori
K
Son
Choel
C
Fujikura
Junji
J
Tomita
Tsutomu
T
Noguchi
Michio
M
Ariyasu
Hiroyuki
H
Takaya
Kazuhiko
K
Masuzaki
Hiroaki
H
Ogawa
Yoshihiro
Y
Hayashi
Tatsuya
T
Inoue
Gen
G
Akamizu
Takashi
T
Hosoda
Hiroshi
H
Kojima
Masayasu
M
Itoh
Hiroshi
H
Toyokuni
Shinya
S
Kangawa
Kenji
K
Nakao
Kazuwa
K
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
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