Sánchez-Margalet Víctor, González-Yanes Carmen, Najib Souad, Santos-Alvarez José
Department of Medical Biochemistry and Molecular Biology, School of Medicine, Virgen Macarena University Hospital, University of Seville, Spain.
Regul Pept. 2010 Apr 9;161(1-3):8-14. doi: 10.1016/j.regpep.2010.02.005. Epub 2010 Feb 23.
Pancreastatin is one of the regulatory peptides derived from intracellular and/or extracellular processing of chromogranin A, the soluble acidic protein present in the secretory granules of the neuroendocrine system. While the intracellular functions of chromogranin A include formation and maturation of the secretory granule, the major extracellular functions are generation of biologically active peptides with demonstrated autocrine, paracrine or endocrine activities. In this review, we will focus on the metabolic function of one of these peptides, pancreastatin, and the mechanisms underlying its effects. Many different reported effects have implicated PST in the modulation of energy metabolism, with a general counterregulatory effect to that of insulin. Pancreastatin induces glycogenolysis in liver and lipolysis in adipocytes. Metabolic effects have been confirmed in humans. Moreover, naturally occurring human variants have been found, one of which (Gly297Ser) occurs in the functionally important carboxy-terminus of the peptide, and substantially increases the peptide's potency to inhibit cellular glucose uptake. Thus, qualitative hereditary alterations in pancreastatin's primary structure may give rise to interindividual differences in glucose and lipid metabolism. Pancreastatin activates a receptor signaling system that belongs to the seven-spanning transmembrane receptor coupled to a Gq-PLCbeta-calcium-PKC signaling pathway. Increased pancreastatin plasma levels, correlating with catecholamines levels, have been found in insulin resistance states, such as gestational diabetes or essential hypertension. Pancreastatin plays important physiological role in potentiating the metabolic effects of catecholamines, and may also play a pathophysiological role in insulin resistance states with increased sympathetic activity.
胰抑制素是一种调节肽，由嗜铬粒蛋白A经细胞内和/或细胞外加工而成，嗜铬粒蛋白A是神经内分泌系统分泌颗粒中存在的可溶性酸性蛋白。嗜铬粒蛋白A的细胞内功能包括分泌颗粒的形成和成熟，而其主要的细胞外功能是产生具有自分泌、旁分泌或内分泌活性的生物活性肽。在这篇综述中，我们将聚焦于这些肽之一的胰抑制素的代谢功能及其作用机制。许多不同的报道效应表明胰抑制素参与能量代谢的调节，其作用总体上与胰岛素相反。胰抑制素可诱导肝脏中的糖原分解和脂肪细胞中的脂肪分解。其代谢效应已在人体中得到证实。此外，还发现了天然存在的人类变体，其中一种（Gly297Ser）出现在该肽功能重要的羧基末端，大大增加了该肽抑制细胞葡萄糖摄取的能力。因此，胰抑制素一级结构的定性遗传改变可能导致个体间葡萄糖和脂质代谢的差异。胰抑制素激活一种受体信号系统，该系统属于与Gq-PLCβ-钙-PKC信号通路偶联的七跨膜受体。在胰岛素抵抗状态，如妊娠期糖尿病或原发性高血压中，已发现胰抑制素血浆水平升高，且与儿茶酚胺水平相关。胰抑制素在增强儿茶酚胺的代谢作用方面发挥重要的生理作用，在交感神经活动增强的胰岛素抵抗状态中也可能发挥病理生理作用。
