文章基本信息

标题：The Insulinostatic Effect of Ghrelin Requires MRAP2 Expression in δ Cells
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作者：Terry C. Yin ; Casey J. Bauchle ; Alix A.J. Rouault 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：6
页码：1-10
DOI：10.1016/j.isci.2020.101216
语种：English
出版社：Elsevier
摘要：SummaryGhrelin regulates both energy intake and glucose homeostasis. In the endocrine pancreas, ghrelin inhibits insulin release to prevent hypoglycemia during fasting. The mechanism through which this is accomplished is unclear, but recent studies suggest that ghrelin acts on δ cells to stimulate somatostatin release, which in turn inhibits insulin release from β cells. Recently, the Melanocortin Receptor Accessory Protein 2 (MRAP2) was identified as an essential partner of the ghrelin receptor (GHSR1a) in mediating the central orexigenic action of ghrelin. In this study we show that MRAP2 is expressed in islet δ cells and is required for ghrelin to elicit a calcium response in those cells. Additionally, we show that both global and δ cell targeted deletion of MRAP2 abrogates the insulinostatic effect of ghrelin. Together, these findings establish that ghrelin signaling within δ cells is essential for the inhibition of insulin release and identify MRAP2 as a regulator of insulin secretion.Graphical AbstractDisplay OmittedHighlights•δ Cells are responsible for the action of ghrelin in the endocrine pancreas•MRAP2 is expressed in multiple cell types in the endocrine pancreas including δ cells•MRAP2 is required for GHSR1a signaling in δ cells•Deletion of MRAP2 results in loss of ghrelin-mediated inhibition of insulin secretionMolecular Biology; Endocrinology