Growth Hormone-Releasing Hormone in Diabetes.
Growth Hormone-Releasing Hormone in Diabetes.
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DOI：
10.3389/fendo.2016.00129
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发表时间：
2016
影响因子：
5.2
通讯作者：
Philipson LH
中科院分区：
文献类型：
--
作者：
Fridlyand LE;Tamarina NA;Schally AV;Philipson LH
生长激素释放激素（GHRH）由下丘脑产生，刺激垂体前叶生长激素的合成和释放。此外，GHRH是许多细胞和器官中细胞功能的重要调节剂。GHRH G蛋白偶联受体（GHRHR）的表达已被证明在不同的外周组织和细胞类型，包括胰岛。在外周活性中，最近的研究表明GHRH类似物具有增加和保持分离胰岛中β细胞的胰岛素分泌的新能力，这使得它们可能用于糖尿病治疗。本文综述了GHRHR在β细胞中的作用，并介绍了独特的工程GHRH激动剂和拮抗剂用于治疗2型糖尿病。我们讨论了GHRHR在垂体生长激素细胞和胰腺β细胞中激活的信号通路的相似性，以及GHRHR通路如何与葡萄糖和其他促分泌素相互作用以刺激胰岛素分泌的可能途径。我们还考虑了新的GHRHR激动剂可以通过保护胰腺β细胞的功能和存活来改善2型糖尿病中的葡萄糖代谢的假设。新的GHRH激动剂的伤口愈合和心脏保护作用表明，它们可能有助于改善某些糖尿病并发症。这些发现突出了GHRHR活性调节剂在糖尿病及其并发症新治疗方法开发中的未来潜在治疗效果。
Growth hormone-releasing hormone (GHRH) is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition, GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR) has been demonstrated in different peripheral tissues and cell types, including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggest that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications.
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DOI：
10.1073/pnas.1121075109
发表时间：
2012-02-07
影响因子：
11.1
作者：
Lucas, Rudolf;Sridhar, Supriya;Schally, Andrew V.
通讯作者：
Schally, Andrew V.
影响因子：
10.8
作者：
Granata, Riccarda;Trovato, Letizia;Ghigo, Ezio
通讯作者：
Ghigo, Ezio
影响因子：
2.2
作者：
Fridlyand LE;Philipson LH
通讯作者：
Philipson LH
影响因子：
4
作者：
BAILEY, CJ;WILKES, LC;BUCHANAN, KD
通讯作者：
BUCHANAN, KD
影响因子：
15.9
作者：
FROHMAN, LA;DOWNS, TR;FELIX, AM
通讯作者：
FELIX, AM