Bang Angela S, Soule Steven G, Yandle Tim G, Richards A Mark, Pemberton Chris J
Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, New Zealand.
J Endocrinol. 2007 Feb;192(2):313-23. doi: 10.1677/JOE-06-0021.
Ghrelin is a 28 amino acid stomach peptide, derived from proghrelin(1-94), that stimulates GH release, appetite and adipose deposition. Recently, a peptide derived from proghrelin(53-75) -- also known as obestatin -- has been reported to be a physiological antagonist of ghrelin in the rat. Using four specific RIAs, we provide the first characterisation of proghrelin(1-94) peptides in human plasma, their modulation by metabolic manipulation and their distribution in mammalian tissues. ghrelin(1-28) immunoreactivity (IR) in human plasma and rat plasma/stomach consisted of major des-octanoyl and minor octanoylated forms, as determined by HPLC/RIA. Human plasma ghrelin(1-28) IR was significantly suppressed by food intake, oral glucose and 1 mg s.c. glucagon administration. ghrelin(1-28) IR and proghrelin(29-94) IR peptide distributions in the rat indicated that the stomach and gastrointestinal tract contain the highest amounts of the peptides. Human and rat plasma and rat stomach extracts contained a major IR peak of proghrelin(29-94)-like peptide as determined by HPLC/RIA, whereas no obestatin IR was observed. Human plasma proghrelin(29-94)-like IR positively correlated with ghrelin(1-28) IR, was significantly suppressed by food intake and oral glucose and shared with ghrelin(1-28) IR a negative correlation with body mass index. We found no evidence for the existence of obestatin as a unique, endogenous peptide. Rather, our data suggest that circulating and stored peptides derived from the carboxyl terminal of proghrelin (C-ghrelin) are consistent in length with proghrelin(29-94) and respond to metabolic manipulation, at least in man, in similar fashion to ghrelin(1-28).
胃饥饿素是一种由28个氨基酸组成的胃肽，由胃饥饿素原（1 - 94）衍生而来，可刺激生长激素释放、增进食欲并促进脂肪沉积。最近，有报道称一种由胃饥饿素原（53 - 75）衍生的肽——也被称为肥胖抑制素——在大鼠体内是胃饥饿素的生理拮抗剂。我们使用四种特异性放射免疫分析法，首次对人血浆中的胃饥饿素原（1 - 94）肽进行了表征，研究了其在代谢调控下的变化以及在哺乳动物组织中的分布情况。通过高效液相色谱/放射免疫分析法测定，人血浆和大鼠血浆/胃中的胃饥饿素（1 - 28）免疫反应性（IR）主要由去辛酰化形式和少量辛酰化形式组成。食物摄入、口服葡萄糖以及皮下注射1毫克胰高血糖素均可显著抑制人血浆中的胃饥饿素（1 - 28）IR。大鼠体内胃饥饿素（1 - 28）IR和胃饥饿素原（29 - 94）IR肽的分布表明，胃和胃肠道中这些肽的含量最高。通过高效液相色谱/放射免疫分析法测定，人和大鼠血浆以及大鼠胃提取物中均含有一个主要的胃饥饿素原（29 - 94）样肽的IR峰，而未观察到肥胖抑制素IR。人血浆中胃饥饿素原（29 - 94）样IR与胃饥饿素（1 - 28）IR呈正相关，受食物摄入和口服葡萄糖显著抑制，且与胃饥饿素（1 - 28）IR一样与体重指数呈负相关。我们没有发现肥胖抑制素作为一种独特的内源性肽存在的证据。相反，我们的数据表明，源自胃饥饿素原羧基末端的循环和储存肽（C - 胃饥饿素）长度与胃饥饿素原（29 - 94）一致，并且至少在人类中，对代谢调控的反应方式与胃饥饿素（1 - 28）相似。
