Ghrelin differentially modulates glucose-induced insulin secretion according to feeding status in sheep.
The present study was conducted to investigate roles of ghrelin in glucose-induced insulin secretion in fasting- and meal-fed state in sheep. Castrated Suffolk rams were fed a maintenance diet of alfalfa hay cubes once a day. Hyperglycemic clamp (HGC) was carried out to examine glucose-induced insulin response from 48 to 53 h (fasting state) and from 3 to 8 h (meal-fed state) after feeding in Experiment 1 and 2 respectively. Total dose of 70 nmol/kg body weight of D-Lys3-GHRP6, a GH secretagogue receptor 1a (GHS-R1a) antagonist, was intravenously administered at 0, 60, and 120 min after the commencement of HGC. In the fasting state, the ghrelin antagonist significantly (P < 0.01) enhanced glucose-induced insulin secretion. In the meal-fed state, i.v. administration of synthetic ovine ghrelin (0.04 microg/kg body weight per min during HGC) significantly (P < 0.05) enhanced glucose-induced insulin secretion. d-Lys3-GHRP6 treatment suppressed ghrelin-induced enhancement of the insulin secretion. In conclusion, ghrelin has an inhibitory and stimulatory role in glucose-induced insulin secretion via GHS-R1a in fasting- and meal-fed state respectively.
Takahashi
Hideyuki
H
School of Veterinary Medicine and Animal Science, Kitasato University, Towada-shi, Aomori 034-8628, Japan.
Kurose
Yohei
Y
Sakaida
Muneyuki
M
Suzuki
Yoshihiro
Y
Kobayashi
Shigeki
S
Sugino
Toshihisa
T
Kojima
Masayasu
M
Kangawa
Kenji
K
Hasegawa
Yoshihisa
Y
Terashima
Yoshiaki
Y
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005215:Fasting / Q000502:physiology*; D054439:Ghrelin / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D054440:Receptors, Ghrelin / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D012756:Sheep
D001786:Blood Glucose; C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D007328:Insulin; D009842:Oligopeptides; D054440:Receptors, Ghrelin; D013006:Growth Hormone; D005947:Glucose