Development of a parallel reaction monitoring-MS method to quantify IGF proteins in dogs and a case of nonislet cell tumor hypoglycemia

Alberto Valdés, Moira Lewitt, Erica Wiss, Margareta Ramström, Emma M. Strage

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)18-29
Number of pages12
JournalJournal of Proteome Research
Volume18
Issue number1
DOIs
Publication statusPublished - 30 Oct 2018

Fingerprint

Hypoglycemia
Insulin-Like Growth Factor II
Dogs
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 3
Neoplasms
Proteins
IGF Type 1 Receptor
Immunoassay
Biological Availability
Canidae
Cats
Insulin
proinsulin-like growth factor II
Growth
Serum

Keywords

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

Cite this

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title = "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.",
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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. / Valdés, Alberto; Lewitt, Moira; Wiss, Erica; Ramström, Margareta; Strage, Emma M.

In: Journal of Proteome Research, Vol. 18, No. 1, 30.10.2018, p. 18-29.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Development of a parallel reaction monitoring-MS method to quantify IGF proteins in dogs and a case of nonislet cell tumor hypoglycemia

AU - Valdés, Alberto

AU - Lewitt, Moira

AU - Wiss, Erica

AU - Ramström, Margareta

AU - Strage, Emma M.

PY - 2018/10/30

Y1 - 2018/10/30

N2 - 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.

AB - 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.

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KW - IGF system

KW - PRM

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