Insulin-like growth factor binding protein-3 (IGFBP-3) is a 264-amino acid peptide (MW 29 kD) produced by the liver as well as other tissues. It is the most abundant of a group of IGFBPs that transport, and control bioavailability and half-life of insulin-like growth factors (IGF), in particular IGF-I, the major mediator of the anabolic- and growth-promoting effects of growth hormone (GH).1 The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II, thus prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Most of the IGFBP-3 in plasma is present as the high molecular weight ternary complex, however, small amounts of free IGFBP-3 are also found.2,3

IGFBP-3 also exhibits intrinsic growth-regulating effects that are not yet fully understood, but have evoked interest with regards to a possible role of IGFBP-3 as a prognostic tumor marker. Low IGFBP-3 and IGF-I levels are observed in GH deficiency or GH resistance,4 also epidemiologic studies suggest that low IGFBP-3 is associated with greater risk of aggressive, metastatic prostate cancers.5 The elevated serum IGFBP-3 and IGF-I levels indicate a sustained overproduction of GH, or excessive rhGH therapy. Both conditions are associated with generalized organomegaly,6 hypertension,7 diabetes,8 cardiomyopathy,9 osteoarthritis,10 and diminished longevity.

The Ansh Labs Intact IGFBP-3 Assay uses an acidification and neutralization method to dissociate Intact IGFBP-3 from all the binding subunits. Intact IGFBP-3 levels are quantified in the extracted samples using a highly sensitive and specific Intact IGFBP-3 ELISA. Total IGFBP-3 levels can be measured using Total IGFBP-3 ELISA (AL-120).

The concentration of bioactive IGF-I, total IGFBP-3 and intact IGFBP-3 in biological fluid can be measured accurately using immunoassay methods (Bioactive IGF-1 ELISA; AL-122, IGF-I inhibition mAb capture and IGF-1 C-terminal mAb) detection; Total IGFBP-3 ELISA; AL-120, C-terminal IGFBP-3 capture and detection mAb; and Intact IGFBP-3 ELISA; AL-149, C-terminal mAb capture and N-terminal mAb detection, respectively). The ratio of total to Intact IGFBP-3 concentration measured in individual subject over time will help normalizes the IGFBP-3 variability between subjects. The immunoassay methods designed for the measurement of bioactive IGF-I, total and Intact IGFBP-3 in patient samples could be of practical value for the diagnosis or prediction of various pathologies including growth abnormalities and cancer.

References:
1. Hwa V, Oh Y, Rosenfeld RG. The insulin-like growth factor-binding protein (IGFBP) superfamily, Endocr Rev. 1999 Dec;20 (6):761-87.
2. Baxter RC, Martin J : Radioimmunassay of growth hormone-dependent insulin-like growth factor binding protein in human plasma. J Clin Invest 1986, 78:1504-1512
3. Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeissel HJ, Bierich JR. A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency. J Clin Endocrinol Metab, 1990, 70:1292-1298
4. Wetterau L, Cohen P: Role of insulin-like growth factor monitoring in optimizing growth hormone therapy. J Ped Endocrinol Metab 2000;13:1371-1376
5. Cancer Res August 1, 2011 71;5154 IGFBP-3 Is a Metastasis Suppression Gene in Prostate Cancer
6. Parama C, Fluiters E, de la Fuente J, et al: Monitoring of treatment success in patients with acromegaly: the value of serum insulin-like growth factor binding protein-3 and serum leptin measurements in comparison to plasma insulin-like growth factor 1 determination. Metabolism 2001; 50: 1117-1121.
7. Watanabe T1, Itokawa M, Nakagawa Y, Iguchi T, Katagiri T. Increased levels of insulin-like growth factor binding protein-3 in hypertensive patients with carotid atherosclerosis. Am. J. Hypertens. 2003 Sep; 16 (9 Pt 1):754-60.
8. Kim MS, Lee DY. Serum insulin-like growth factor-binding protein-3 level correlated with glycemic control and lipid profiles in children and adolescents with type 1 diabetes. J Pediatr Endocrinol Metab. 2014 Sep 20;27(9-10):857-61. doi: 10.1515/jpem-2013-0358.
9. Granata R, Broglio F, Migliorino D, Cutrupi S, Baldanzi G, Sireno M, Fubini A, Grazian A, Ghigo E, Pucci A. Neonatal and adult human heart tissues from normal subjects and patients with ischemic, dilated or hypertrophic cardiomyopathy express insulin-like growth factor binding protein-3 (IGFBP-3). J Endocrinol Invest. 2000 Dec;23(11):724-6.
10. Lee HS, Woo SJ, Koh HW, Ka SO, Zhou L, Jang KY, Lim HS, Kim HO, Lee SI, Park BH. Regulation of apoptosis and inflammatory responses by insulin-like growth factor binding protein 3 in fibroblast-like synoviocytes and experimental animal models of rheumatoid arthritis. Arthritis Rheumatol. 2014 Apr;66(4):863-73. doi: 10.1002/art.38303.
11. HHS Publication, 5th ed., 2007. Biosafety in Microbiological and Biomedical Laboratories. Available http://www.cdc.gov/biosafety/publications/bmbl5/BMBL5
12. DHHS (NIOSH) Publication No. 78–127, August 1976. Current Intelligence Bulletin 13 – Explosive Azide Hazard. Available http:// www.cdc.gov/niosh.
13. Kricka L. Interferences in immunoassays – still a threat. Clin Chem 2000; 46: 1037–1038.

IGFBP-3 (Intact) ELISA AL-149

Kumar A, Kalra B, Kommareddy V, Chowdavarapu K, Mistry S, Savjani G, Oxvig C. Development of Well Characterized ELISAs for Bound and Unbound Insulin-Like Growth Factors and their Binding Proteins. Poster presented at 98th Annual Endocrine Society Meeting; 2016 Apr 1-3; Boston, MA.

All Products Cited: IGF-I ELISA AL-121; Free IGF-I ELISA AL-122; IGF-II ELISA AL-131; IGFBP-2 ELISA AL-140; Intact IGFBP-3 ELISA AL-149; Total IGFBP-3 ELISA AL-120; Total IGFBP-4 ELISA AL-126; Intact IGFBP-4 ELISA AL-128; IGFBP-5 ELISA AL-127

Polyzos SA, Perakakis N, Boutari C, Kountouras J, Ghaly W, Anastasilakis AD, Karagiannis A, Mantzoros CS. Targeted Analysis of Three Hormonal Systems Identifies Molecules Associated with the Presence and Severity of NAFLD. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e390–400. doi: 10.1210/clinem/dgz172. PMID: 31690932;
PMCID: PMC7112980.

All Products Cited: GLP-1 ELISA AL-172; GLP-2 ELISA AL-174; Glucagon ELISA AL-157; MPGF ELISA AL-175; Oxyntomodulin ELISA AL-139; Follistatin-Like 3 ELISA AL-152; Activin B ELISA AL-150; IGF-I ELISA AL-121; Total IGFBP-3 ELISA AL-120; Intact IGFBP-3 ELISA AL-149; Total IGFBP-4 ELISA AL-126; Intact IGFBP-4 ELISA AL-128; picoPAPP-A ELISA AL-101

Fujimoto M, Andrew M, Liao L, Zhang D, Yildirim G, Sluss P, Kalra B, Kumar A, Yakar S, Hwa V, Dauber A. Low IGF-I Bioavailability Impairs Growth and Glucose Metabolism in a Mouse Model of Human PAPPA2 p.Ala1033Val Mutation. Endocrinology. 2019 Jun 1;160(6):1363-1376. doi: 10.1210/en.2018-00755.

All Products Cited: IGF-I Free (Rat/Mouse) ELISA; IGF-I Total (Rat/Mouse) ELISA; IGFBP-3 (Intact) ELISA AL-149

Fujimoto M, Khoury JC, Khoury PR, Kalra B, Kumar A, Sluss P, Oxvig C, Hwa V, Dauber A. Anthropometric and biochemical correlates of PAPP-A2, free IGF-I, and IGFBP-3 in childhood. European journal of endocrinology, 182(3), 363–374. https://doi.org/10.1530/EJE-19-0859

All Products Cited: Total IGF-I AL-121; Free IGF-I AL-122; Total IGFBP-3 AL-120; Intact IGFBP-3 AL-149; PAPP-A2 AL-109

Anastasilakis AD, Koulaxis D, Upadhyay J, Pagkalidou E, Kefala N, Perakakis N, Polyzos SA, Economou F, Mantzoros CS. Free IGF-1, Intact IGFBP-4, and PicoPAPP-A are Altered in Acute Myocardial Infarction Compared to Stable Coronary Artery Disease and Healthy Controls. Horm Metab Res. 2019 Feb;51(2):112-119.

All Products Cited: IGF-I ELISA AL-121; IGF-I (Free) ELISA AL-122; IGFBP-3 (Total) ELISA AL-120; IGFBP-3 (Intact) ELISA AL-149; IGFBP-4 (Intact) ELISA AL-128; IGFBP-4 (Total) ELISA AL-126; PAPP-A ELISA AL-101

IGFBP-3 (Total) ELISA AL-120

Donegan D, Bale LK, Conover CA. PAPP-A in normal human mesangial cells: effect of inflammation and factors related to diabetic nephropathy. J Endocrinol. 2016 Oct;231(1):71-80. doi: 10.1530/JOE-16-0205. Epub 2016 Aug 12. PMID: 27519211.

All Products Cited: PAPP-A ELISA AL-106; IGFBP-3 ELISA AL-120; IGFBP-4 ELISA AL-126; IGFBP-5 ELISA AL-127; IGF-I ELISA AL-121; IGF-II ELISA AL-131

Anastasilakis AD, Koulaxis D, Upadhyay J, Pagkalidou E, Kefala N, Perakakis N, Polyzos SA, Economou F, Mantzoros CS. Free IGF-1, Intact IGFBP-4, and PicoPAPP-A are Altered in Acute Myocardial Infarction Compared to Stable Coronary Artery Disease and Healthy Controls. Horm Metab Res. 2019 Feb;51(2):112-119.

All Products Cited: IGF-I ELISA AL-121; IGF-I (Free) ELISA AL-122; IGFBP-3 (Total) ELISA AL-120; IGFBP-3 (Intact) ELISA AL-149; IGFBP-4 (Intact) ELISA AL-128; IGFBP-4 (Total) ELISA AL-126; PAPP-A ELISA AL-101

Dauber A, Munoz-Calvo MT, Barrios V, Domene HM, Kloverpris S, Serra-Juhe C, Desikan V, Pozo J, Muzumdar R, Martos-Moreno GA, Hawkins F, Jasper HG, Conover CA, Frystyk J, Yakar S, Hwa V, Chowen JA, Oxvig C, Rosenfeld RG, Perez-Jurado LA, Argente J. Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability. EMBO Mol Med. 2016 Mar 31;8(4):363-74.

All Products Cited: IGF-I ELISA AL-121; Free IGF-I ELISA AL-122; IGFBP-3 ELISA AL-120; IGFBP-5 ELISA AL-127; PAPP-A2 AL-109

Guercio BJ, Zhang S, Ou FS, et al. . IGF-Binding Proteins, Adiponectin, and Survival in Metastatic Colorectal Cancer: Results From CALGB (Alliance)/SWOG 80405. JNCI Cancer Spectr. 2020 Aug 27;5(1):pkaa074. doi: 10.1093/jncics/pkaa074

All Products Cited: IGFBP-3 (Total) ELISA AL-120; C-Peptide of Insulin ELISA AL-151; IGF-I ELISA AL-121

Kumar A, Kalra B, Kommareddy V, Chowdavarapu K, Mistry S, Savjani G, Oxvig C. Development of Well Characterized ELISAs for Bound and Unbound Insulin-Like Growth Factors and their Binding Proteins. Poster presented at 98th Annual Endocrine Society Meeting; 2016 Apr 1-3; Boston, MA.

All Products Cited: IGF-I ELISA AL-121; Free IGF-I ELISA AL-122; IGF-II ELISA AL-131; IGFBP-2 ELISA AL-140; Intact IGFBP-3 ELISA AL-149; Total IGFBP-3 ELISA AL-120; Total IGFBP-4 ELISA AL-126; Intact IGFBP-4 ELISA AL-128; IGFBP-5 ELISA AL-127

Fujimoto M, Khoury JC, Khoury PR, Kalra B, Kumar A, Sluss P, Oxvig C, Hwa V, Dauber A. Anthropometric and biochemical correlates of PAPP-A2, free IGF-I, and IGFBP-3 in childhood. European journal of endocrinology, 182(3), 363–374. https://doi.org/10.1530/EJE-19-0859

All Products Cited: Total IGF-I AL-121; Free IGF-I AL-122; Total IGFBP-3 AL-120; Intact IGFBP-3 AL-149; PAPP-A2 AL-109

Polyzos SA, Perakakis N, Boutari C, Kountouras J, Ghaly W, Anastasilakis AD, Karagiannis A, Mantzoros CS. Targeted Analysis of Three Hormonal Systems Identifies Molecules Associated with the Presence and Severity of NAFLD. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e390–400. doi: 10.1210/clinem/dgz172. PMID: 31690932;
PMCID: PMC7112980.

All Products Cited: GLP-1 ELISA AL-172; GLP-2 ELISA AL-174; Glucagon ELISA AL-157; MPGF ELISA AL-175; Oxyntomodulin ELISA AL-139; Follistatin-Like 3 ELISA AL-152; Activin B ELISA AL-150; IGF-I ELISA AL-121; Total IGFBP-3 ELISA AL-120; Intact IGFBP-3 ELISA AL-149; Total IGFBP-4 ELISA AL-126; Intact IGFBP-4 ELISA AL-128; picoPAPP-A ELISA AL-101

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