Ghrelin Regulates Insulin Release and Glycemia: Physiological Role and Therapeutic Potential
Ghrelin Regulates Insulin Release and Glycemia: Physiological Role and Therapeutic Potential
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DOI：
10.2174/157339908783502352
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Kakei, Masafumi
中科院分区：
文献类型：
--
作者：
Yada, Toshihiko;Dezaki, Katsuya;Kakei, Masafumi
葡萄糖刺激胰岛β细胞释放胰岛素。激素和神经物质增强或抑制葡萄糖诱导的胰岛素释放。 Ghrelin 是一种从胃中分离出来的新型酰化 28 个氨基酸肽，是生长激素 (GH) 促分泌素受体 (GHS-R) 的内源性配体。循环中的生长素释放肽主要在胃中产生。生长素释放肽是 GH 释放和摄食的有效刺激剂，并表现出积极的心血管作用。关于葡萄糖代谢，初步研究表明，低血浆生长素释放肽水平与空腹胰岛素水平升高、胰岛素抵抗和肥胖有关。最近的研究表明，生长素释放肽通过 GTP 结合蛋白的 G α(i2) 亚型和延迟的 K + (Kv) 通道抑制葡萄糖诱导的胰岛素释放，这代表了一种新的信号传导机制，并且源自胰岛的生长素释放肽可调节胰岛素释放，从而调节血糖。此外，消除生长素释放肽可增强胰岛素释放，从而预防或改善高脂肪饮食喂养的小鼠和ob/ob小鼠的葡萄糖耐受不良。本综述重点关注 ghrelin 在调节胰岛素释放和血糖中的生理作用、ghrelin 在胰岛 β 细胞中的胰岛素抑制机制，以及 ghrelin-GHS-R 系统作为治疗 2 型糖尿病的治疗靶点的潜力。
Insulin release from pancreatic islet beta-cells is stimulated by glucose. Glucose-induced insulin release is potentiated or suppressed by hormones and neural substances. Ghrelin, a novel acylated 28-amino acid peptide isolated from stomach, is the endogenous ligand for the growth hormone (GH) secretagogue-receptor (GHS-R). Circulating ghrelin is produced predominantly in stomach. Ghrelin is a potent stimulator of GH release and feeding as well as exhibiting positive cardiovascular effects. In relation to the glucose metabolism, initial studies indicated that low plasma ghrelin levels are associated with elevated fasting insulin levels, insulin resistance, and obesity. It has recently been demonstrated that ghrelin suppresses glucose-induced insulin release via G alpha(i2) subtype of GTP-binding proteins and delayed outward K + (Kv) channels, representing a novel signaling mechanism, and that the ghrelin originating from islets regulates insulin release and thereby glycemia. Furthermore, elimination of ghrelin enhances insulin release to prevent or ameliorate glucose intolerance in high-fat diet fed mice and ob/ob mice. This review focuses on the physiological roles of ghrelin in regulating insulin release and glycemia, the insulinostatic mechanisms of ghrelin in islet beta-cells, and the potential of ghrelin-GHS-R system as the therapeutic target to treat type 2 diabetes.