Bandyopadhyay Gautam K, Mahata Sushil K
Department of Medicine, University of California San Diego , La Jolla, CA , USA.
Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Medicine, Metabolic Physiology and Ultrastructural Biology Laboratory, VA San Diego Healthcare System, San Diego, CA, USA.
Front Endocrinol (Lausanne). 2017 Feb 8;8:20. doi: 10.3389/fendo.2017.00020. eCollection 2017.
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 (-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.
嗜铬粒蛋白A（CgA）是一种前激素和颗粒生成因子，存在于内分泌和神经内分泌组织以及神经元中，具有受调控的分泌途径。CgA的细胞内功能包括致密核心颗粒生物发生的起始和调控以及神经内分泌细胞中激素的隔离。这种蛋白质与分泌的激素共同储存和共同释放。CgA的细胞外功能包括生物活性肽的生成，如胰抑制素（PST）、血管抑制素、WE14、抑制素（CST）和丝氨酸蛋白酶抑制剂。CgA基因敲除小鼠（-KO）表现出：（i）伴有血浆儿茶酚胺增加的高血压，（ii）肥胖，（iii）肝脏胰岛素敏感性提高，以及（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，更多研究表明，促炎的PST会影响胰岛素敏感性和葡萄糖耐量，而CST则可减轻肥胖和高血压。本综述将聚焦于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用途。
