Takahashi H, Kurose Y, Kobayashi S, Sugino T, Kojima M, Kangawa K, Hasegawa Y, Terashima Y
School of Veterinary Medicine and Animal Science, Kitasato University, Towada-shi, Aomori 034-8628, Japan.
J Endocrinol. 2006 Apr;189(1):67-75. doi: 10.1677/joe.1.06310.
The purpose of this study was to investigate the effects of physiologic levels of ghrelin on insulin secretion and insulin sensitivity (glucose disposal) in scheduled fed-sheep, using the hyperglycemic clamp and hyperinsulinemic euglycemic clamp respectively. Twelve castrated Suffolk rams (69.8 +/- 0.6 kg) were conditioned to be fed alfalfa hay cubes (2% of body weight) once a day. Three hours after the feeding, synthetic ovine ghrelin was intravenously administered to the animals at a rate of 0.025 and 0.05 mug/kg body weight (BW) per min for 3 h. Concomitantly, the hyperglycemic clamp or the hyperinsulinemic euglycemic clamp was carried out. In the hyperglycemic clamp, a target glucose concentration was clamped at 100 mg/100 ml above the initial level. In the hyperinsulinemic euglycemic clamp, insulin was intravenously administered to the animals for 3 h at a rate of 2 mU/kg BW per min. Basal glucose concentrations (44+/- 1 mg/dl) were maintained by variably infusing 100 mg/dl glucose solution. In both clamps, plasma ghrelin concentrations were dose-dependently elevated and maintained at a constant level within the physiologic range. Ghrelin infusions induced a significant (ANOVA; P < 0.01) increase in plasma GH concentrations. In the hyperglycemic clamp, plasma insulin levels were increased by glucose infusion and were significantly (P < 0.05) greater in ghrelin-infused animals. In the hyperinsulinemic euglycemic clamp, glucose infusion rate, an index of insulin sensitivity, was not affected by ghrelin infusion. In conclusion, the present study has demonstrated for the first time that ghrelin enhances glucose-induced insulin secretion in the ruminant animal.
本研究的目的是分别使用高血糖钳夹技术和正常血糖高胰岛素钳夹技术，研究生理水平的胃饥饿素对定时喂食绵羊胰岛素分泌和胰岛素敏感性（葡萄糖处置）的影响。选用12只去势的萨福克公羊（体重69.8±0.6千克），使其适应每天喂食一次苜蓿干草块（体重的2%）。喂食3小时后，以每分钟0.025和0.05微克/千克体重的速率给动物静脉注射合成羊胃饥饿素，持续3小时。同时，进行高血糖钳夹或正常血糖高胰岛素钳夹。在高血糖钳夹中，将目标血糖浓度钳夹在比初始水平高100毫克/100毫升处。在正常血糖高胰岛素钳夹中，以每分钟2毫单位/千克体重的速率给动物静脉注射胰岛素3小时。通过可变输注100毫克/分升葡萄糖溶液维持基础血糖浓度（44±1毫克/分升）。在两种钳夹中，血浆胃饥饿素浓度均呈剂量依赖性升高，并在生理范围内维持恒定水平。胃饥饿素输注导致血浆生长激素（GH）浓度显著升高（方差分析；P<0.01）。在高血糖钳夹中，葡萄糖输注使血浆胰岛素水平升高，且在输注胃饥饿素的动物中显著更高（P<0.05）。在正常血糖高胰岛素钳夹中，作为胰岛素敏感性指标的葡萄糖输注速率不受胃饥饿素输注的影响。总之，本研究首次证明胃饥饿素可增强反刍动物中葡萄糖诱导的胰岛素分泌。
