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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
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
Univ West Scotland, Sch Hlth & Life Sci, Paisley PA1 2BE, Renfrew, Scotland.
Albano Anim Hosp, S-18236 Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
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2019 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 18, no 1, p. 18-29Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC , 2019. Vol. 18, no 1, p. 18-29
Keywords [en]
big IGF-II, dog NICTH, IGF system, PRM, targeted proteomics
National Category
Clinical Science
Identifiers
URN: urn:nbn:se:uu:diva-375230DOI: 10.1021/acs.jproteome.8b00259ISI: 000455285900003PubMedID: 30376339OAI: oai:DiVA.org:uu-375230DiVA, id: diva2:1283676
Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2019-01-29Bibliographically approved

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