Sánchez-Margalet V, González-Yanes C
Department of Medical Biochemistry and Molecular Biology, School of Medicine, Investigation Unit of the University Hospital Virgen Macarena, Seville 41009, Spain.
Am J Physiol. 1998 Dec;275(6):E1055-60. doi: 10.1152/ajpendo.1998.275.6.E1055.
Pancreastatin (PST), a regulatory peptide with a general inhibitory effect on secretion, is derived from chromogranin A, a glycoprotein present throughout the neuroendocrine system. We have previously demonstrated the counterregulatory role of PST on insulin action in rat hepatocytes. Here, we are reporting the PST effects on rat adipocytes. PST dose dependently inhibits basal and insulin-stimulated glucose transport, lactate production, and lipogenesis, impairing the main metabolic actions of insulin in adipocytes. These effects were observed in a wide range of insulin concentrations, leading to a shift to the right in the dose-response curve. Maximal effect was observed at 10 nM PST, and the IC50 value was approximately 1 nM. Moreover, PST has a lipolytic effect in rat adipocytes (ED50 0.1 nM), although it was completely inhibited by insulin. In contrast, PST dose dependently stimulated protein synthesis and enhanced insulin-stimulated protein synthesis. In summary, these data show the lipokinetic effect of PST and the inhibitory effect of PST on insulin metabolic action within a range of physiological concentrations. Therefore, these results give new pathophysiological basis for the association of PST with insulin resistance.
胰抑制素（PST）是一种对分泌具有普遍抑制作用的调节肽，它由嗜铬粒蛋白A衍生而来，嗜铬粒蛋白A是一种存在于整个神经内分泌系统中的糖蛋白。我们之前已经证明了PST在大鼠肝细胞中对胰岛素作用的反调节作用。在此，我们报告PST对大鼠脂肪细胞的影响。PST剂量依赖性地抑制基础和胰岛素刺激的葡萄糖转运、乳酸生成及脂肪生成，损害胰岛素在脂肪细胞中的主要代谢作用。在广泛的胰岛素浓度范围内均观察到了这些效应，导致剂量反应曲线向右移动。在10 nM PST时观察到最大效应，IC50值约为1 nM。此外，PST对大鼠脂肪细胞具有脂解作用（ED50为0.1 nM），尽管它被胰岛素完全抑制。相反，PST剂量依赖性地刺激蛋白质合成并增强胰岛素刺激的蛋白质合成。总之，这些数据显示了PST在生理浓度范围内的脂肪动力学效应以及对胰岛素代谢作用的抑制作用。因此，这些结果为PST与胰岛素抵抗的关联提供了新的病理生理学基础。
