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

Abstract

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.

Keywords

big IGF-II; dog NICTH; IGF system; PRM; targeted proteomics

Published in

Journal of Proteome Research
2019, volume: 18, number: 1, pages: 18-29
Publisher: AMER CHEMICAL SOC

SLU Authors

• Strage, Emma

  • Department of Clinical Sciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Clinical Science

Publication identifier

• DOI: https://doi.org/10.1021/acs.jproteome.8b00259

Permanent link to this page (URI)

https://res.slu.se/id/publ/98066