Colombo Michele, Gregersen Søren, Xiao Jianzhong, Hermansen Kjeld
Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, Aarhus University, Denmark.
Pancreas. 2003 Aug;27(2):161-6. doi: 10.1097/00006676-200308000-00009.
Ghrelin, a neuropeptide containing 28 amino acids, shows a reciprocal diurnal plasma fluctuation to that of plasma insulin. The aim of this study is to clarify the dose and glucose-dependency of ghrelin on the insulin secretion and to compare its effect with that of other neuropeptides-GLP-1, CART (55-102), CART (55-76), CART (62-76), MCH, orexin A, and B.
Rat islets were incubated with 1 pmol/l-1 micromol/l of ghrelin, CART fragments, MCH, orexin A or B, or GLP-1 (n = 16-32) in the presence of 16.7 mmol/l glucose. Ghrelin (10 nmol/l) was added to islets at glucose concentrations of 3.3, 6.6, 16.7 and 25 mmol/l, respectively (n = 28-32). Also, INS-1E cells were incubated with ghrelin (1 nmol/l) in the presence of glucose (3.3, 6.6, 16.7, and 25 mmol/l). In addition, we measured the mRNA expression of the ghrelin receptor using RT-PCR.
Ghrelin inhibited insulin secretion from islets and INS-1E cells in a dose- and glucose-dependent manner. Neither 10 pmol/l-1 micromol/l of CART fragments, MCH, orexin A, nor orexin B changed the insulin secretion at 16.7 mmol/l glucose, while GLP-1, as expected, stimulated the insulin release from rat islets. Interestingly, ghrelin receptors were expressed both in islets, INS-1E, MIN 6 and alpha cell Tca-9 lines.
Ghrelin inhibits the insulin secretion in vitro in a dose- and glucose-dependent manner. Beta cells contain ghrelin receptors. CART fragments did not affect the insulin secretion. Ghrelin may play a physiological role for the regulation of insulin secretion.
胃饥饿素是一种含28个氨基酸的神经肽，其血浆水平呈现与血浆胰岛素相反的昼夜波动。本研究旨在阐明胃饥饿素对胰岛素分泌的剂量依赖性和葡萄糖依赖性，并将其作用与其他神经肽——胰高血糖素样肽-1（GLP-1）、可卡因-安非他明调节转录肽（CART，55-102）、CART（55-76）、CART（62-76）、黑素细胞刺激素（MCH）、食欲素A和食欲素B进行比较。
将大鼠胰岛与1 pmol/l至1 μmol/l的胃饥饿素、CART片段、MCH、食欲素A或B或GLP-1（n = 16 - 32）在16.7 mmol/l葡萄糖存在的情况下进行孵育。分别在葡萄糖浓度为3.3、6.6、16.7和25 mmol/l时向胰岛中添加10 nmol/l的胃饥饿素（n = 28 - 32）。此外，将INS-1E细胞与胃饥饿素（1 nmol/l）在葡萄糖（3.3、6.6、16.7和25 mmol/l）存在的情况下进行孵育。另外，我们使用逆转录聚合酶链反应（RT-PCR）测量胃饥饿素受体的mRNA表达。
胃饥饿素以剂量和葡萄糖依赖性方式抑制胰岛和INS-1E细胞的胰岛素分泌。在16.7 mmol/l葡萄糖水平下，10 pmol/l至1 μmol/l的CART片段、MCH、食欲素A和食欲素B均未改变胰岛素分泌，而正如预期的那样，GLP-1刺激大鼠胰岛释放胰岛素。有趣的是，胃饥饿素受体在胰岛、INS-1E、MIN 6和α细胞Tca-9系中均有表达。
胃饥饿素在体外以剂量和葡萄糖依赖性方式抑制胰岛素分泌。β细胞含有胃饥饿素受体。CART片段不影响胰岛素分泌。胃饥饿素可能在胰岛素分泌调节中发挥生理作用。
