Dezaki Katsuya, Yada Toshihiko
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Japan.
Methods Enzymol. 2012;514:317-31. doi: 10.1016/B978-0-12-381272-8.00020-9.
Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach, where circulating ghrelin is produced predominantly. In addition to its unique role in regulating growth-hormone release, mealtime hunger, lipid metabolism, and the cardiovascular system, ghrelin is involved in the regulation of glucose metabolism. Ghrelin is expressed in pancreatic islets and released into pancreatic microcirculations. Ghrelin inhibits insulin release in mice, rats, and humans. Pharmacological and genetic blockades of islet-derived ghrelin markedly augment glucose-induced insulin release. The signal transduction mechanisms of ghrelin in islet β-cells are very unique, being distinct from those utilized for growth-hormone release. Ghrelin attenuates the glucose-induced cAMP production and PKA activation, which drives activation of Kv channels and suppression of the glucose-induced Ca(2+) increase and insulin release in β-cells. Insulinostatic function of the ghrelin-GHS-R system in islets is a potential therapeutic target for type 2 diabetes.
胃泌素，一种酰化的28个氨基酸的肽，是从胃中分离出来的，循环中的胃泌素主要在胃中产生。除了在调节生长激素释放、进餐时的饥饿感、脂质代谢和心血管系统方面具有独特作用外，胃泌素还参与葡萄糖代谢的调节。胃泌素在胰岛中表达并释放到胰腺微循环中。胃泌素在小鼠、大鼠和人类中抑制胰岛素释放。胰岛来源的胃泌素的药理学和基因阻断显著增强葡萄糖诱导的胰岛素释放。胃泌素在胰岛β细胞中的信号转导机制非常独特，与用于生长激素释放的机制不同。胃泌素减弱葡萄糖诱导的cAMP产生和PKA激活，这驱动Kv通道的激活并抑制β细胞中葡萄糖诱导的[Ca(2+)]i增加和胰岛素释放。胰岛中胃泌素-GHS-R系统的胰岛素稳定功能是2型糖尿病的一个潜在治疗靶点。
