PMID- 31493625 OWN - NLM STAT- MEDLINE DCOM- 20200512 LR - 20200518 IS - 1532-2238 (Electronic) IS - 1096-6374 (Linking) VI - 48-49 DP - 2019 Oct-Dec TI - The insulin-like growth factor-I receptor stimulating activity (IRSA) in health and disease. PG - 16-28 LID - S1096-6374(19)30038-3 [pii] LID - 10.1016/j.ghir.2019.08.001 [doi] AB - Determination of true IGF-I bioactivity in serum and other biological fluids is still a substantial challenge. The IGF-IR Kinase Receptor Activation assay (IGF-IR KIRA assay) is a novel tool to asses IGF-IR stimulating activity (IRSA) and has opened a new era in studying the IGF system. In this paper we discuss many studies showing that measuring IRSA by the IGF-IR KIRA assay often provides fundamentally different information about the IGF system than the commonly used total IGF-I immunoassays. With the IGF-IR KIRA assay phosphorylation of tyrosine residues of the IGF-IR is used as read out to quantify IRSA in unknown (serum) samples. The IGF-IR KIRA assay gives information about net overall effects of circulating IGF-I, IGF-II, IGFBPs and IGFBP-proteases on IGF-IR activation and seems especially superior to immunoreactive total IGF-I in monitoring therapeutic interventions. Although the IRSA as measured by the IGF-IR KIRA assay probably more closely reflects true bioactive IGF-I than measurements of total IGF-I in serum, the IGF-IR KIRA assay in its current form does not give information about all the post-receptor intracellular events mediated by the IGF-IR. Interestingly, in several conditions in health and disease IRSA measured by the IGF-IR KIRA assay is considerably higher in interstitial fluid and ascites than in serum. This suggests that both the paracrine (local) and endocrine (circulating) IRSA should be measured to get a complete picture about the role of the IGF system in health and disease. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Janssen, Joseph A M J L AU - Janssen JAMJL AD - Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, the Netherlands. Electronic address: j.a.m.j.l.janssen@erasmusmc.nl. FAU - Varewijck, Aimee J AU - Varewijck AJ AD - Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, the Netherlands. FAU - Brugts, Michael P AU - Brugts MP AD - Department of Internal Medicine, Ikazia Hospital, Rotterdam, the Netherlands. LA - eng PT - Journal Article PT - Review DEP - 20190821 PL - Scotland TA - Growth Horm IGF Res JT - Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society JID - 9814320 RN - 0 (IGF1 protein, human) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 2.7.10.1 (Receptor, IGF Type 1) SB - IM MH - Disease/*etiology MH - Humans MH - Insulin-Like Growth Factor I/*metabolism MH - Receptor, IGF Type 1/*metabolism MH - Signal Transduction OTO - NOTNLM OT - Disease OT - Endocrine OT - Health OT - IGF-I OT - IGF-I bioactivity OT - IGF-I receptor OT - Immunoassays OT - KIRA OT - Paracrine EDAT- 2019/09/08 06:00 MHDA- 2020/05/19 06:00 CRDT- 2019/09/08 06:00 PHST- 2019/03/15 00:00 [received] PHST- 2019/07/26 00:00 [revised] PHST- 2019/08/19 00:00 [accepted] PHST- 2019/09/08 06:00 [pubmed] PHST- 2020/05/19 06:00 [medline] PHST- 2019/09/08 06:00 [entrez] AID - S1096-6374(19)30038-3 [pii] AID - 10.1016/j.ghir.2019.08.001 [doi] PST - ppublish SO - Growth Horm IGF Res. 2019 Oct-Dec;48-49:16-28. doi: 10.1016/j.ghir.2019.08.001. Epub 2019 Aug 21.