Measurement of Free Insulin-Like Growth Factor-I Using Immunoradiometric Assay

Takada, Makoto; Nakanome, Hiroyuki; Kishida, Mariko; Hirose, Sohichi; Hasegawa, Tomonobu; Hasegawa, Yukihiro

doi:10.1080/15321819408009577

Cited by 49 publications

(30 citation statements)

References 11 publications

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“…In this study of healthy adult subjects, we found acute changes in the IGF-I system involving not only IGFBP-1, but also IGFBP-3 and free IGF-I. Basal values for these parameters were similar to those reported by others (4,10,(15)(16)(17). We used a single injection of insulin after an iv bolus of glucose that triggered a physiological insulin release, and we obtained a well characterized blood glucose pattern with an early peak and a nadir by 60 min followed by a rapid recovery (11).…”

Section: Discussionsupporting

confidence: 72%

Free Insulin-Like Growth Factor I (IGF-I) in Healthy Subjects: Relationship with IGF-Binding Proteins and Insulin Sensitivity

Nyomba

Berard

Murphy

1997

The Journal of Clinical Endocrinology & Metabolism

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The majority of insulin-like growth factor I (IGF-I) circulates in blood bound to a family of IGF-binding proteins (IGFBPs). Only a small fraction of IGF-I is unbound or free, and one of the postulated roles of the IGFBPs is regulation of this free component, thereby increasing IGF-I bioavailability. Whether free IGF-I plays a physiological role in glucose homeostasis, however, is not clear. In this study, we examined the effects of acute changes in serum insulin on free IGF-I, total IGF-I, IGFBP-1, and IGFBP-3 in 11 healthy subjects. Glucose (0.3 g/kg) and insulin (0.05 U/kg) were injected iv at 0 and 20 min, respectively. Blood samples were drawn at defined intervals for 3 h, and insulin sensitivity (S I ) was computed by Bergman's minimal model. Serum insulin reached a first peak after glucose injection and a second, higher peak after exogenous insulin administration. Although the total IGF-I level remained constant for the duration of the experiment, free IGF-I decreased by 20% 20 min after the first insulin peak and by 35% 20 min after the second peak. IGFBP-1 first declined to 20% below basal, then rose to 3-fold the basal level. IGFBP-3 increased linearly to 20% above basal by the end of the experiment, and this increase mirrored the decline of free IGF-I. In the fasting state, free IGF-I was positively correlated with S I (r ϭ 0.52; P Ͻ 0.005) and inversely correlated with glucose (r ϭ Ϫ0.51; P Ͻ 0.005) and IGFBP-1 (r ϭ Ϫ0.65; P Ͻ 0.001). In conclusion, free IGF-I is acutely regulated by insulin and correlates with S I , suggesting that it may play a physiological role in glucose homeostasis. (J Clin Endocrinol Metab 82: [2177][2178][2179][2180][2181] 1997) T HE REGULATION of blood glucose is a complex phenomenon that involves insulin-mediated glucose disposal by muscle, fat, and liver (the classic target tissues for insulin) and noninsulin-dependent glucose utilization by the brain and splanchnic tissues (1). The effects of insulin are opposed by multiple counterregulatory hormones. Insulinlike growth factor I (IGF-I) and IGF-II are structurally similar to proinsulin and functionally similar to insulin (2). Administration of recombinant human IGF-I has been shown to induce hypoglycemia even in the absence of endogenous insulin (3). Most IGFs circulate in blood bound to a family of IGF-binding proteins (IGFBPs), six of which have been cloned and sequenced (4). These IGFBPs have been shown to be released by several cell types and may either augment or inhibit the actions of the IGFs. IGFBP-1 and IGFBP-3 are the best characterized of the six circulating IGFBPs. IGFBP-3 is classically considered to be a reservoir transporting IGFs in the blood stream in a 150-kDa complex that also includes the liver-derived acid-labile subunit.Recently, IGFBP-3 has been shown to undergo partial proteolysis under certain conditions, and this is believed to increase circulating free IGFs and promote IGF bioavailability (5). However, IGFBP-1 is the sole binding protein that has been unequivocally demonstrated to mod...

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Section: Discussionsupporting

confidence: 72%

Free Insulin-Like Growth Factor I (IGF-I) in Healthy Subjects: Relationship with IGF-Binding Proteins and Insulin Sensitivity

Nyomba

Berard

Murphy

1997

The Journal of Clinical Endocrinology & Metabolism

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“…Hizuka et al reported that free IGF-I levels increased during pregnancy [18]. Recently, an increase in the free IGF-I level in pregnant women, determined by a newly developed immunoradiometric assay, was also reported by our group [19,20]. It is therefore important to check the proteolytic activity in sera to understand the action of IGFs in various physiological conditions.…”

Section: 8=476%)mentioning

confidence: 99%

Proteolytic Activity of IGFBP-3 in Various Clinical Conditions During Childhood Studied by Means of Western Immunoblotting.

Hasegawa

Koni

et al. 1995

Endocr J

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“…Biological potency of serum GH was determined using an Nb2 cell-proliferation assay, as described previously [14]. Serum total and free IGF-1 were measured by an immunoradiometric assay (IRMA) (Chiba-Corning, Tokyo) [15]. Serum IGFBP-3 was measured by the RIA method [16, 17][Diagnostic Systems Laboratories (DSL), Tokyo].…”

Section: Methodsmentioning

confidence: 99%

Near-Normal Linear Growth in the Setting of Markedly Reduced Growth Hormone and IGF-1

Murashita

Tajima²,

Nakae³

et al. 1999

Horm Res Paediatr

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A 14.2-year-old prepubertal boy diagnosed with complete-type growth hormone deficiency and tertiary hypothyroidism, keeps growing in the height range between –1 and –2 SD. He has been treated with levothyroxine only. To understand the growth mechanism of this boy, we analyzed the serum growth hormone (GH) with a radioimmunoassay (RIA), serum GH bioactivity with Nb2 and erythroid progenitor cell bioassays, and growth hormone-binding protein (GHBP) with a ligand-mediated immunofunctional assay (LIFA). In addition, IGF-1 and free IGF-1 were analyzed by immunoradiometric assay (IRMA) and insulin-like growth factor-binding protein-3 (IGFBP-3) by Western immunoblot. Peak GH-RIA responses to insulin, arginine and GH-releasing factor, and nocturnal GH secretion, were low (0.5–2.3 ng/ml); bioactive GH was low (0.313 ng/ml), and GHBP was elevated (84 ng/ml). The serum levels of IGF-1 and free IGF-1 were continuously low, 17.1–39.3 and 0.17–0.26 ng/ml, respectively. Moreover, serum IGFBP-3 levels were low (1.68– 1.39 mg/l) and IGFBP-3 protease activity was negative. Prolactin and insulin were in the normal range. The result of the assay for growth-promoting activity showed that the patient’s serum stimulated normal erythroid progenitor cells twice as potently as did healthy thin adult control serum. These results suggest that GH and IGF-1 are not indispensable for maintaining physical growth in this boy. Thus, it appears that circulating GH and IGF-1 are not mandatory requirements for maintaining normal physical growth, and other, as yet uncharacterized, pathways or growth factors might be sufficiently compensatory under certain conditions.

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Measurement of Free Insulin-Like Growth Factor-I Using Immunoradiometric Assay

Cited by 49 publications

References 11 publications

Free Insulin-Like Growth Factor I (IGF-I) in Healthy Subjects: Relationship with IGF-Binding Proteins and Insulin Sensitivity

Free Insulin-Like Growth Factor I (IGF-I) in Healthy Subjects: Relationship with IGF-Binding Proteins and Insulin Sensitivity

Proteolytic Activity of IGFBP-3 in Various Clinical Conditions During Childhood Studied by Means of Western Immunoblotting.

Near-Normal Linear Growth in the Setting of Markedly Reduced Growth Hormone and IGF-1

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