The Role of Insulin-Like Growth Factor Binding Proteins

Holly, Jeff M.P.; Perks, Claire M

doi:10.1159/000095523

Cited by 122 publications

(115 citation statements)

References 87 publications

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“…However, serum IGFBP-2 levels are not indicative of an increased cancer risk because in these tumors, serum IGFBP-2 levels are generally normal before the diagnosis of cancer (12,30). Clinical data are paralleled by many in vitro studies, also showing IGFBP-2 overexpression in various different cancer cell lines (31).…”

Section: Discussionmentioning

confidence: 99%

Elevated serum levels of IGF-binding protein 2 in patients with non-seminomatous germ cell cancer: correlation with tumor markers α-fetoprotein and human chorionic gonadotropin

Fottner

Sattarova

Hoffmann

et al. 2008

European Journal of Endocrinology

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Background/aims: Alterations of the IGF system have been described in several different types of cancer. However, no information is available about the role of the IGF system in patients with nonseminomatous germ cell cancer. Methods: Free IGF-I, IGF-II, acid-labile subunit, and IGF-binding proteins (IGFBPs) 1-4 were analyzed by specific RIAs in 32 patients with untreated non-seminomas and compared with IGFBP levels of 38 healthy controls. Serum IGFBPs were analyzed by western ligand blotting (WLB) and immunoblotting. In 16 patients, IGFBP profiles were measured before, during, and after treatment. Results: In patients with testicular cancer, IGF-II levels were on average 1.44-fold higher than in the healthy control group (1027G48 ng/ml versus 711G30 ng/ml, P!0.0001). IGFBP-2 levels were on average 2.6-fold higher (586G58 ng/ml versus 226G17 ng/ml, P!0.001). During follow-up, a decrease in IGFBP-2 levels was observed in all successfully treated patients, which correlated closely with a decrease in the tumor markers a-fetoprotein and human chorionic gonadotropin. Additionally, in all patients with recurrent disease, a significant further increase in IGFBP-2 levels (from 358G97 to 976G 260 ng/ml) was detected. IGFBP-3 levels, as measured by RIA, were not different in patients with testicular cancer compared with controls. However, WLB analysis demonstrated markedly decreased intact IGFBP-3 bands in untreated patients and a significant increase after successful therapy. Conclusion: Our results demonstrate that markedly elevated IGF-II and IGFBP-2 serum levels in patients with non-seminomatous germ cell cancer, showing a significant decrease after successful therapy and an increase in recurrent disease. Additionally, indirect evidence points to an increased proteolytic activity for IGFBP-3 in untreated testicular cancer patients.

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Section: Discussionmentioning

confidence: 99%

Elevated serum levels of IGF-binding protein 2 in patients with non-seminomatous germ cell cancer: correlation with tumor markers α-fetoprotein and human chorionic gonadotropin

Fottner

Sattarova

Hoffmann

et al. 2008

European Journal of Endocrinology

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“…IGFBP-1 is synthesized in the liver, where its expression is under the control of insulin which suppresses its production (74). It has also been suggested that GH directly regulates IGFBP-1 secretion (75).…”

Section: Regulation Of Gh Secretionmentioning

confidence: 99%

Genetic disorders in the GH–IGF-I axis in mouse and man

Walenkamp

Wit²

2007

eur j endocrinol

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Animal knockout experiments have offered the opportunity to study genes that play a role in growth and development. In the last few years, reports of patients with genetic defects in GH-IGF-I axis have greatly increased our knowledge of genetically determined causes of short stature. We will present the animal data and human reports of genetic disorders in the GH-IGF-I axis in order to describe the role of the GH-IGF-I axis in intrauterine and postnatal growth. In addition, the effects of the GH-IGF-I axis on the development and function of different organ systems such as brain, inner ear, eye, skeleton, glucose homeostasis, gonadal function, and immune system will be discussed. The number of patients with genetic defects in the GH-IGF-I axis is small, and a systematic diagnostic approach and selective genetic analysis in a patient with short stature are essential to identify more patients. Finally, the implications of a genetic defect in the GH-IGF-I axis for the patient and the therapeutic options will be discussed.European Journal of Endocrinology 157 S15-S26

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“…A possible mechanism linking disturbed sleep to metabolic disturbances, which has not yet been investigated, may be insulin-like growth factor-binding proteins (IGFBPs), proteins in the circulation that bind IGFs (IGF1 and IGF2) and determine the bioavailability of these factors, as well as having direct effects themselves (4). IGFBP1 secretion in humans is mainly regulated at transcriptional level by insulin (5) and also by other counterregulatory hormones like glucocorticoids (6) and growth hormone (GH).…”

Section: Introductionmentioning

confidence: 99%

Sleeping during the day: effects on the 24-h patterns of IGF-binding protein 1, insulin, glucose, cortisol, and growth hormone

Rehman¹,

Brismar²,

Holmbäck³

et al. 2010

European Journal of Endocrinology

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Background: Disturbed sleep is a major risk factor for metabolic disturbances, including type 2 diabetes, but the involved mechanisms are still poorly understood. We investigated how an acute shift of sleep to the daytime affected IGF-binding protein 1 (IGFBP1), which is a risk factor for diabetes. Methods: Seven healthy men (age, 22-32 years) participated in a night sleep condition (sleep 2300-0700 h) and a day sleep condition (0700-1500 h) with hourly blood samples taken for 25 h (starting at 1900 h) and isocaloric meals every 4th hour awake. The blood samples were analyzed for IGFBP1, insulin, GH, glucose, and cortisol. Result: The acute shift of sleep and meal timing (to 8 h) shifted the 24-h patterns of IGFBP1, glucose, insulin, and GH to a similar degree. However, the day sleep condition also resulted in elevated levels of IGFBP1 (area under curve (AUC)C22%, P!0.05), and reduced glucose levels (AUCK7%, P!0.05) compared with nocturnal sleep. Sleeping during the day resulted in elevated cortisol levels during early sleep and reduced levels in late sleep, but also in increased levels the subsequent evening (P's!0.05). Conclusion: Sleep-fasting seems to be the primary cause for the elevation of IGFBP1, irrespective of sleep timing. However, sleeping during the day resulted in higher levels of IGFBP1 than nocturnal sleep, suggesting altered metabolism among healthy individuals, which may have implications for other groups with altered sleep/eating habits such as shift workers. Moreover, sleep and meal times should be accounted for while interpreting IGFBP1 samples.

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The Role of Insulin-Like Growth Factor Binding Proteins

Cited by 122 publications

References 87 publications

Elevated serum levels of IGF-binding protein 2 in patients with non-seminomatous germ cell cancer: correlation with tumor markers α-fetoprotein and human chorionic gonadotropin

Elevated serum levels of IGF-binding protein 2 in patients with non-seminomatous germ cell cancer: correlation with tumor markers α-fetoprotein and human chorionic gonadotropin

Genetic disorders in the GH–IGF-I axis in mouse and man

Sleeping during the day: effects on the 24-h patterns of IGF-binding protein 1, insulin, glucose, cortisol, and growth hormone

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