Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion
Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion
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DOI：
10.1530/eje.0.1460241
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发表时间：
2002-02-01
影响因子：
5.8
通讯作者：
Marco, J
中科院分区：
文献类型：
--
作者：
Egido, EM;Rodríguez-Gallardo, J;Marco, J
目的：Ghrelin是在人和大鼠胃中鉴定的28个氨基酸残基的肽，其作为GH促分泌素受体（GHS-R）的内源性配体并刺激GH释放。GHS-R在许多组织中表达，包括胰腺，并且ghrelin样免疫反应性存在于外周血浆中，其中其水平在禁食期间增加并在食物摄入后降低。营养状况和循环ghrelin浓度之间的关系促使我们研究这种肽对胰腺激素分泌的影响。结果：在灌流液中加入10 nM ghrelin可显著降低胰岛素对葡萄糖、精氨酸和卡巴胆碱的反应，以及生长抑素对精氨酸的反应。Ghrelin对这种氨基酸诱导的胰高血糖素输出没有影响。在较低的浓度（2 nM）ghrelin也被发现抑制葡萄糖诱导的insulin release.Conclusion：这些研究结果支持的建议，即ghrelin对胰岛素释放的抑制作用构成了补调节的B细胞，有助于抑制其分泌活动的状态下的食物剥夺。另一方面，生长激素释放肽对胰腺生长抑素释放的抑制表明这种激素对广泛分布的D细胞群的阻断作用。
Objective: Ghrelin is a 28 amino acid residue peptide identified in both human and rat stomach and which acts as an endogenous ligand for the GH secretagogue receptor (GHS-R) and stimulates GH release. GHS-Rs are expressed in a number of tissues, including the pancreas, and ghrelin-like immunoreactivity is present in peripheral plasma, where its levels increase during fasting and decrease after food intake. The relationship between nutritional status and circulating ghrelin concentrations prompted us to investigate the effect of this peptide on pancreatic hormone secretion.Methods: The study was performed in the isolated rat pancreas perfused in situ. Insulin, glucagon and somatostatin were measured by radioimmunoassay.Results: Addition of 10 nM ghrelin to the perfusate significantly reduced the insulin response to the secretagogues glucose, arginine and carbachol, which act on the B-cell via different mechanisms, as well as the somatostatin response to arginine. Ghrelin was without effect on the glucagon output induced by this amino acid. At a lower concentration (2 nM) ghrelin was also found to inhibit glucose-induced insulin release.Conclusion: These findings support the proposal that the inhibitory effect of ghrelin on insulin release constitutes a tonic regulation of the B-cell, contributing to restrain its secretory activity in the state of food deprivation. On the other hand, the inhibition of pancreatic somatostatin release by ghrelin suggests a blocking effect of this hormone on the widely distributed D-cell population.