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首页> 外文期刊>Cell metabolism >LEAP2 Is an Endogenous Antagonist of the Ghrelin Receptor
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LEAP2 Is an Endogenous Antagonist of the Ghrelin Receptor

机译：Leap2是Ghrelin受体的内源性拮抗剂

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Ghrelin, an appetite-stimulatory hormone secreted by the stomach, was discovered as a ligand for the growth hormone secretagogue receptor (GHSR). Through GHSR, ghrelin stimulates growth hormone (GH) secretion, a function that evolved to protect against starvation-induced hypoglycemia. Though the biology mediated by ghrelin has been described in great detail, regulation of ghrelin action is poorly understood. Here, we report the discovery of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous antagonist of GHSR. LEAP2 is produced in the liver and small intestine, and its secretion is suppressed by fasting. LEAP2 fully inhibits GHSR activation by ghrelin and blocks the major effects of ghrelin in vivo, including food intake, GH release, and maintenance of viable glucose levels during chronic caloric restriction. In contrast, neutralizing antibodies that block endogenous LEAP2 function enhance ghrelin action in vivo. Our findings reveal a mechanism for fine-tuning ghrelin action in response to changing environmental conditions.
机译：Ghrelin是胃分泌的食欲刺激激素，被发现为生长激素促泌糖基因受体（GHSR）的配体。通过GHSR，Ghrelin刺激生长激素（GH）分泌，一种演变以防止饥饿诱导的低血糖的功能。虽然已经详细描述了Ghrelin介导的生物学，但Ghrelin行动的调节很难理解。在此，我们将肝脏表达的抗微生物肽2（LEAP2）的发现作为GHSR的内源拮抗剂的发现。 Leap2在肝脏和小肠中产生，并且通过禁食抑制其分泌。 Leap2通过Ghrelin完全抑制GHSR活化，并阻断Ghrelin在体内的主要影响，包括食物摄入，GH释放和维持慢性热量限制期间活葡萄糖水平。相比之下，中和抗体阻断内源性沸腾功能增强体内Ghrelin作用。我们的调查结果揭示了一种微调Ghrelin行动的机制，以应对不断变化的环境条件。

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