Takahashi Hideyuki, Kurose Yohei, Sakaida Muneyuki, Suzuki Yoshihiro, Kobayashi Shigeki, Sugino Toshihisa, Kojima Masayasu, Kangawa Kenji, Hasegawa Yoshihisa, Terashima Yoshiaki
School of Veterinary Medicine and Animal Science, Kitasato University, Towada-shi, Aomori 034-8628, Japan.
J Endocrinol. 2007 Sep;194(3):621-5. doi: 10.1677/JOE-07-0206.
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.
本研究旨在探讨胃饥饿素在绵羊空腹和进食状态下对葡萄糖诱导的胰岛素分泌中的作用。对去势的萨福克公羊每天饲喂一次苜蓿干草块维持日粮。在实验1和实验2中，分别在喂食后48至53小时（空腹状态）和3至8小时（进食状态）进行高血糖钳夹（HGC）以检测葡萄糖诱导的胰岛素反应。在HGC开始后的0、60和120分钟静脉注射70 nmol/kg体重的D-Lys3-GHRP6（一种生长激素促分泌素受体1a（GHS-R1a）拮抗剂）的总剂量。在空腹状态下，胃饥饿素拮抗剂显著（P < 0.01）增强了葡萄糖诱导的胰岛素分泌。在进食状态下，静脉注射合成羊胃饥饿素（HGC期间0.04μg/kg体重每分钟）显著（P < 0.05）增强了葡萄糖诱导的胰岛素分泌。D-Lys3-GHRP6处理抑制了胃饥饿素诱导的胰岛素分泌增强。总之，胃饥饿素在空腹和进食状态下分别通过GHS-R1a对葡萄糖诱导的胰岛素分泌具有抑制和刺激作用。
