Development of a Parallel Reaction Monitoring-MS Method To Quantify IGF Proteins in Dogs and a Case of Nonislet Cell Tumor Hypoglycemia.,Journal of Proteome Research

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Development of a Parallel Reaction Monitoring-MS Method To Quantify IGF Proteins in Dogs and a Case of Nonislet Cell Tumor Hypoglycemia.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2018-10-30 , DOI: 10.1021/acs.jproteome.8b00259
Alberto Valdés ₁ , Moira Lewitt ₂ , Erica Wiss ₃ , Margareta Ramström ₁ , Emma M Strage

Affiliation

Nonislet-cell tumor hypoglycemia (NICTH) is a rare paraneoplastic phenomenon well described in dogs and humans. Tumors associated with NICTH secrete incompletely processed forms of insulin-like growth factor-II (IGF-II), commonly named big IGF-II. These forms have increased bioavailability and interact with the insulin and IGF-I receptor causing hypoglycemia and growth-promoting effects. Immunoassays designed for human samples have been used to measure canine IGF-I and -II, but they possess some limitations. In addition, there are no validated methods for measurement of big IGF-II in dogs. In the present study, a targeted parallel reaction monitoring MS-based method previously developed for cats has been optimized and applied to simultaneously quantify the serum levels of IGF-I, IGF-II, and IGFBP-3, and for the first time, the levels of big IGF-II in dogs. This method allows the absolute quantification of IGF proteins using a mixture of QPrEST proteins previously designed for humans. The method possesses good linearity and repeatability and has been used to evaluate the IGF-system in a dog with NICTH syndrome. In this dog, the levels of big IGF-II decreased by 80% and the levels of IGF-I and IGFBP-3 increased approximately 20- and 4-times, respectively, after removal of the tumor.

中文翻译：

平行反应监测-MS方法的发展，以量化狗和非胰岛细胞瘤低血糖症的情况下的狗的IGF蛋白。

非胰岛细胞瘤低血糖症（NICTH）是一种罕见的副肿瘤现象，在狗和人类中都有很好的描述。与NICTH相关的肿瘤分泌的胰岛素样生长因子II（IGF-II）的加工形式不完全，通常被称为大IGF-II。这些形式具有更高的生物利用度，并与胰岛素和IGF-I受体相互作用，引起低血糖症和促进生长的作用。设计用于人体样品的免疫测定法已用于测量犬的IGF-I和-II，但是它们具有一些局限性。此外，尚无用于狗中大IGF-II测定的有效方法。在本研究中，先前为猫开发的基于目标的平行反应监测基于MS的方法已经过优化和应用于同时定量IGF-I，IGF-II和IGFBP-3的血清水平，这是第一次，狗中大IGF-II的水平。该方法允许使用先前为人类设计的QPrEST蛋白混合物对IGF蛋白进行绝对定量。该方法具有良好的线性和可重复性，已被用于评估患有NICTH综合征的狗的IGF系统。在该狗中，切除肿瘤后，大IGF-II的水平下降了80％，而IGF-I和IGFBP-3的水平分别上升了约20倍和4倍。

更新日期：2018-10-31

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