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Journal of Endocrinology (2007) 194, 621-625    DOI: 10.1677/JOE-07-0206
© 2007 Society for Endocrinology
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Ghrelin differentially modulates glucose-induced insulin secretion according to feeding status in sheep

 Hideyuki Takahashi, Yohei Kurose, Muneyuki Sakaida, Yoshihiro Suzuki, Shigeki Kobayashi, Toshihisa Sugino1, Masayasu Kojima2, Kenji Kangawa2, Yoshihisa Hasegawa and Yoshiaki Terashima

School of Veterinary Medicine and Animal Science, Kitasato University, Towada-shi, Aomori 034-8628, Japan
1 Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima-shi, Hiroshima 739-8528, Japan
2 National Cardiovascular Center Research Institute, Osaka 565-8565, Japan

(Correspondence should be addressed to Y Kurose; Email: kurose{at}vmas.kitasato-u.ac.jp)

(M Kojima is currently at the School of Veterinary Medicine and Animal Science, Kitasato University, Towada-Shi, Aamori 034-8628, Japan)

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 µ g/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.






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