Unacylated ghrelin is active on the INS-1E rat insulinoma cell line independently of the growth hormone secretagogue receptor type. la and the corticotropin releasing factor 2 receptor
Unacylated ghrelin is active on the INS-1E rat insulinoma cell line independently of the growth hormone secretagogue receptor type. la and the corticotropin releasing factor 2 receptor
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DOI：
10.1016/j.mce.2006.03.040
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发表时间：
2006-06-07
影响因子：
4.1
通讯作者：
van der Lely, Aart Jan
中科院分区：
文献类型：
--
作者：
Gauna, Carlotta;Delhanty, Patric J. D.;van der Lely, Aart Jan
非酰化Ghrelin(UAG)和酰化Ghrelin(AG)都有代谢作用。为了研究AG和UAG在Ghrelin受体上的相互作用，我们以静态孵育30min后的胰岛素分泌为读数，评价了AG和UAG对INS-1E细胞的作用。此外，还研究了生长激素促分泌素受体Ia(GHS-R1a)或促肾上腺皮质激素释放因子2(CRF2)受体(CRF2R)作为UAG受体的可能参与，测定了它们的mRNA表达以及受体拮抗剂对胰岛素释放的功能影响。UAG和AG均在纳摩尔范围内剂量依赖性地刺激胰岛素释放。两种GHS-R1a拮抗剂([D-Lys 3]GHRP-6和BIM28163)可拮抗AG诱导的胰岛素输出，但不阻断UAG的作用。这些效应发生在低水平的GHS-R1a mRNA存在的情况下。未观察CRF2R表达和CRF2R拮抗剂(ASTRESIN 2B)对胰岛素分泌的影响。总之，我们为UAG的特殊效应提供了一种灵敏且可重复性的检测方法，在本研究中，UAG与INS-1E细胞的胰岛素释放有关。我们的数据支持UAG的特定受体的存在。除CRF2R和GHS-R1a之外。AG对该细胞株胰岛素分泌的刺激作用是通过GHS-R1a介导的。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
Both unacylated ghrelin (UAG) and acylated ghrelin (AG) exert metabolic effects. To investigate the interactions between AG and UAG on ghrelin receptors we evaluated the effects of AG and UAG on INS-1E rat insulinoma cells, using insulin secretion after 30 min static incubation as a read-out. A possible involvement of the growth hormone secretagogue receptor type I a (GHS-R1a) or the corticotropin-releasing factor 2 (CRF2) receptor (CRF2R), as a putative receptor for UAG, was also studied determining their mRNA expression and the functional effects of receptor antagonists on insulin release. Both UAG and AG stimulated insulin release dose-dependently in the nanomolar range. The AG-induced insulin output was antagonized by two GHS-R1a antagonists ([D-Lys 3]GHRP-6 and BIM28163), which did not block UAG actions. These effects occurred in the presence of low levels of GHS-R1a mRNA. Neither CRF2R expression not, effects of the CRF2R antagonist (astressin2B) on insulin output were observed. In conclusion, we provide a sensitive and reproducible assay for specific effects of UAG, which in this study is responsible for insulin release by INS-1E cells. Our data support the existence of a specific receptor for UAG. other than the CRF2R and GHS-R1a. The stimulatory effect on insulin secretion by AG in this cell line is mediated by the GHS-R1a. (c) 2006 Elsevier Ireland Ltd. All rights reserved.