IGFBP-1, an insulin like growth factor binding protein, is a cell growth inhibitor

Liu, L.; Brinkman, Arend; Blat, C.; Harel, L

doi:10.1016/0006-291x(91)91470-w

Cited by 57 publications

(24 citation statements)

References 13 publications

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“…In the circulation of normal, non-pregnant individuals, IGFBP-1 is present as a highly phosphorylated form. Other studies have used either recombinant IGFBP-1 which is non-phosphorylated (Cox et al 1994, Lee et al 1996 or IGFBP-1 purified from amniotic fluid which is deficient in the highly phosphorylated form (Frauman et al 1989, Burch et al 1990, Angervo et al 1991, Liu et al 1991, Lewitt et al 1993. We therefore purified phosphorylated IGFBP-1 from HepG2-conditioned medium and found it was more potent than npIGFBP-1 since it completely reversed the effects of IGF-I at a 1:1 molar ratio, while at this molar ratio npIGFBP-1 did not significantly inhibit IGF mitogenic actions.…”

Section: Discussionmentioning

confidence: 99%

IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte

Siddals¹,

Westwood²,

Gibson³

et al. 2002

Journal of Endocrinology

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IGF action in vivo is acutely regulated by IGF-binding protein-1 (IGFBP-1) and its phosphorylation state is implicated in modulating these effects. Since IGFs have an important regulatory role in adipocyte function, we investigated the effects of phosphorylated IGFBP-1 (pIGFBP-1) and non-phosphorylated IGFBP-1 (npIGF BP-1) on 3T3-L1 preadipocyte proliferation and adipocyte metabolism.IGFs stimulated clonal expansion of 3T3-L1 cells (IGF-I more potently than IGF-II (EC 50 : 30 nM and 50 nM)). npIGFBP-1 inhibited IGF-I (50 nM) clonal expansion at a 5:1 molar ratio (P<0·01), whereas pIGFBP-1 (purified from HepG2 cell medium) abolished clonal expansion at a 1:1 molar ratio (P<0·005). In contrast, IGF-II-induced clonal expansion was inhibited 100% at a 1:1 molar ratio of npIGFBP-1.In mature adipocytes, IGF-I was equipotent with insulin in stimulating glucose uptake (EC 50 : 10 nM) and inhibiting isoproterenol-induced lipolysis (EC 50 : 15 nM). npIGFBP-1 completely reversed IGF-I effects at a 1:1 molar ratio (P<0·01).In summary, IGFs rather than insulin are potent regulators of clonal expansion in 3T3-L1 preadipocytes. Importantly, IGFs are equipotent with insulin in regulating adipocyte metabolism. IGFBP-1 inhibits IGF effects on preadipocyte proliferation and adipocyte metabolism, with pIGFBP-1 being more potent than npIGFBP-1 at inhibiting mitogenic actions. Since IGFBP-1 is acutely regulated by insulin, this could have important consequences in hyperinsulinaemic and insulin-resistant states.

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Section: Discussionmentioning

confidence: 99%

IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte

Siddals¹,

Westwood²,

Gibson³

et al. 2002

Journal of Endocrinology

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“…A number of reports have shown that IGFBP-1 is capable of inhibition as well as augmentation of IGF's bioactivity (15)(16)(17). These apparently paradoxical observations may be explained by the recent findings that differential phosphorylation at three serine residues can significantly alter IGFBP-1's affinity for IGFs (10).…”

Section: Discussionmentioning

confidence: 99%

The phosphorylation status of insulin-like growth factor-binding protein-1 in prepubertal obese children

Kamoda

Saitoh²,

Nakahara³

et al. 1999

European Journal of Endocrinology

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Objective: We measured the total and nonphosphorylated insulin-like growth factor-binding protein (IGFBP)-1 concentrations in obese children to determine the effect of obesity on the status of IGFBP-1 phosphorylation. We also measured the serum levels of insulin, total and free IGF-I, and IGFBP-3 to investigate their relationships to the IGFBP-1 phosphorylation status in obese subjects. Subjects and methods: Nineteen prepubertal obese and 15 age-matched control children were included in the study. The serum levels of total and nonphosphorylated IGFBP-1 were determined by noncompetitive RIAs. Results: The serum levels of total and nonphosphorylated IGFBP-1 were significantly lower in the obese group (48.7 Ϯ 5.6 mg/l, P < 0.001 and 11.1 Ϯ 1.9 mg/l, P < 0.01 respectively) than in the controls (86.7 Ϯ 9.0 mg/l and 28.8 Ϯ 6.2 mg/l respectively). However, the ratio of nonphosphorylated IGFBP-1 to total IGFBP-1 did not differ significantly between the obese and control groups. The circulating free IGF-I level was significantly higher in the obese children than in the controls (P < 0.05), while the serum levels of insulin, total IGF-I and IGFBP-3 were not significantly different between the two groups. A stepwise regression analysis of the combined group revealed that only the total IGFBP-1 level was an independent predictor of the free IGF-I concentration (P < 0.001).Conclusion: The present study shows that both total and nonphosphorylated IGFBP-1 concentrations are decreased in obese children and the increased free IGF-I level in obese children is related to the reduced total IGFBP-1 level, but unrelated to the change in the IGFBP-1 phosphorylation status.

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“…We previously demonstrated that growth hormone (GH) amplifies gonadotropin actions in the process of follicular development and ovulation, at least in part, stimulating ovarian IGF-I production (11). The biological effects of IGF-I are modulated by a family of IGFBPs in a complex and incompletely understood manner (5,(12)(13)(14). In the ovary, IGFBP-3 appears to neutralize the actions of gonadotropin and IGF-I, probably via its ability to sequester IGF-I (12,13,15).…”

Section: Introductionmentioning

confidence: 99%

Interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system in follicular growth and ovulation.

Yoshimura¹,

Aoki²,

Sueoka³

et al. 1996

J. Clin. Invest.

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The interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system (RAS) in follicular growth and ovulation were studied with the use of an isolated perfused rabbit ovary preparation. Ovulation failed to occur in either control ovaries or the experimental ovaries perfused with IGF-I in a concentration of 1, 10, or 100 ng/ml in the absence of gonadotropin. Exposure to IGF-I stimulated the secretion rate of angiotensin II-like immunoreactivity (Ang II-IR) in perfused rabbit ovaries in a dose-dependent manner. The percent increase in follicle diameter in ovaries perfused with IGF-I for 12 h was significantly correlated with the secretion rate of Ang II-IR at 12 h after exposure to IGF-I. The addition of IGFBP-3 to the perfusate did not induce ovulation in the absence of gonadotropin, but exposure to IGFBP-3 inhibited hCG-induced ovulation in a dosedependent manner. In addition, IGFBP-3 significantly reduced the ovarian secretion rate of Ang II-IR and prostaglandins stimulated by hCG administration. Intrafollicular plasminogen activator (PA) activity significantly increased within 4 h after exposure to 100 ng/ml of IGF-I, compared with that in control ovaries perfused with medium alone. The concomitant addition of IGFBP-3 to the perfusate significantly reduced the IGF-I-stimulated PA activity in the preovulatory follicles at 4, 6, and 8 h after exposure to IGF-I. However, IGFBP-3 alone affected neither the ovarian secretion rate of Ang II-IR nor intrafollicular PA activity. Exposure to streptokinase, an exogenous PA, in vitro stimulated both follicular growth and the intrafollicular Ang II-IR content. In conclusion, IGF-I enhances both ovarian Ang II production and follicular development by stimulating intrafollicular PA activity. ( J. Clin. Invest. 1996. 98:308-316.)

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IGFBP-1, an insulin like growth factor binding protein, is a cell growth inhibitor

Cited by 57 publications

References 13 publications

IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte

IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte

The phosphorylation status of insulin-like growth factor-binding protein-1 in prepubertal obese children

Interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system in follicular growth and ovulation.

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