Characterisation of proghrelin peptides in mammalian tissue and plasma
Characterisation of proghrelin peptides in mammalian tissue and plasma
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DOI：
10.1677/joe-06-0021
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发表时间：
2007-02-01
影响因子：
4
通讯作者：
Pemberton, Chris J.
中科院分区：
文献类型：
--
作者：
Bang, Angela S.;Soule, Steven G.;Pemberton, Chris J.
Ghrelin是一种28个氨基酸的胃肽，来源于proghrelin（1-94），刺激GH释放，食欲和脂肪沉积。最近，已报道来源于促生长素释放肽（53-73）的肽-也称为obestatin -是大鼠中促生长素释放肽的生理拮抗剂。使用四种特异性RIA，我们提供了人血浆中促生长素释放肽（1-94）肽的第一个表征，它们通过代谢操作的调节及其在哺乳动物组织中的分布。通过HPLC/RIA测定，人血浆和大鼠血浆/胃中的ghrelin（1-28）免疫反应性（IR）由主要的脱辛酰基和次要的辛酰基化形式组成。人血浆ghrelin（1-28）IR通过食物摄入、口服葡萄糖和1 mg s.c.胰高血糖素给药。在大鼠中生长素释放肽（1-28）IR和前生长素释放肽（29-94）IR肽的分布表明胃和胃肠道含有最高量的肽。通过HPLC/RIA测定，人和大鼠血浆和大鼠胃提取物含有促生长素释放肽（29-94）样肽的主要IR峰，而未观察到obestatin IR。人血浆proghrelin（29-94）样IR与ghrelin（1-28）IR呈正相关，受食物摄入和口服葡萄糖的显著抑制，与ghrelin（1-28）IR共同与体重指数呈负相关。我们没有发现obestatin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，源自促生长素释放肽（C-促生长素释放肽）的羧基末端的循环和储存肽在长度上与促生长素释放肽一致（29-94），并且至少在人中以与促生长素释放肽类似的方式响应代谢操纵（1-28）。
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(53-73) - 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).