Chromogranin A Regulation of Obesity and Peripheral Insulin Sensitivity.
Chromogranin A Regulation of Obesity and Peripheral Insulin Sensitivity.
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DOI：
10.3389/fendo.2017.00020
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发表时间：
2017
影响因子：
5.2
通讯作者：
Mahata SK
中科院分区：
文献类型：
--
作者：
Bandyopadhyay GK;Mahata SK
嗜铬颗粒蛋白A （Chromogranin A, CgA）是内分泌和神经内分泌组织以及神经元中的激素原和颗粒形成因子，具有受调控的分泌途径。CgA的胞内功能包括在神经内分泌细胞中启动和调控密核颗粒的生物生成和激素的固存。这种蛋白质与分泌的激素共同储存和释放。CgA的细胞外功能包括产生生物活性肽，如胰抑素（PST）、血管抑素、WE14、catestatin （CST）和丝氨酸肽。CgA基因敲除小鼠（Chga-KO）表现为：(i)高血压伴血浆儿茶酚胺升高，（ii）肥胖，（iii）肝脏胰岛素敏感性改善，（iv）肌肉胰岛素抵抗。这些发现表明单个cga衍生肽可能调节不同的生理功能。事实上，其他研究表明，促炎的PST影响胰岛素敏感性和葡萄糖耐量，而CST减轻肥胖和高血压。本文将重点介绍PST和CST肽在胰岛素敏感和胰岛素抵抗模型中的不同代谢作用，以及它们作为治疗靶点的潜在应用。
Chromogranin A (CgA) is a prohormone and granulogenic factor in endocrine and neuroendocrine tissues, as well as in neurons, and has a regulated secretory pathway. The intracellular functions of CgA include the initiation and regulation of dense-core granule biogenesis and sequestration of hormones in neuroendocrine cells. This protein is co-stored and co-released with secreted hormones. The extracellular functions of CgA include the generation of bioactive peptides, such as pancreastatin (PST), vasostatin, WE14, catestatin (CST), and serpinin. CgA knockout mice (Chga-KO) display: (i) hypertension with increased plasma catecholamines, (ii) obesity, (iii) improved hepatic insulin sensitivity, and (iv) muscle insulin resistance. These findings suggest that individual CgA-derived peptides may regulate different physiological functions. Indeed, additional studies have revealed that the pro-inflammatory PST influences insulin sensitivity and glucose tolerance, whereas CST alleviates adiposity and hypertension. This review will focus on the different metabolic roles of PST and CST peptides in insulin-sensitive and insulin-resistant models, and their potential use as therapeutic targets.