Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein (IGFBP)-3, Phosphoisoforms of IGFBP-1 and Postnatal Growth in Very-Low-Birth-Weight Infants

Kajantie, Eero

doi:10.1159/000074513

Cited by 19 publications

(23 citation statements)

References 48 publications

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“…Such an approach to study the significance of IGFBP-1 phosphorylation clinically has not been achievable so far. This study establishes a framework on which biological fluids/clinical samples could be used in ascertaining correlations of IGFBP-1 phosphorylation with fetal outcomes as yet ambiguous in FGR (16,17,19,43). The current strategy is also broadly pertinent for other clinically and functionally relevant proteins regulated by phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Functional and Complementary Phosphorylation State Attributes of Human Insulin-like Growth Factor-Binding Protein-1 (IGFBP-1) Isoforms Resolved by Free Flow Electrophoresis

Nissum

Shehab²,

Sukop

et al. 2009

Molecular & Cellular Proteomics

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Fetal growth restriction (FGR) is a common disorder in119 . Our data demonstrate that phosphorylation at Ser 119 plays a significant role in modulating affinity of IGFBP-1 for IGF-I. In addition, an altered profile of IGFBP-1 phosphoisoforms was revealed between FGR and healthy pregnancies that may result from potential site-specific phosphorylation. This study provides a strong basis for use of this novel approach in establishing the linkage between phosphorylation of IGFBP-1 and FGR. This overall strategy will also be broadly applicable to other phosphoproteins with clinical and functional significance.

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Section: Discussionmentioning

confidence: 99%

Functional and Complementary Phosphorylation State Attributes of Human Insulin-like Growth Factor-Binding Protein-1 (IGFBP-1) Isoforms Resolved by Free Flow Electrophoresis

Nissum

Shehab²,

Sukop

et al. 2009

Molecular & Cellular Proteomics

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show abstract

“…In particular, insulin-like growth factors (IGF) and the epidermal growth factor (EGF) were found in physiological concentrations. IGFs are the postnatal mediators of the effect of growth hormone on child growth [28,29,30]. IGF-II and IGFBP-2 were found in higher concentrations than IGF-I and IGFBP-3 in human milk, even though the latter dominate in blood serum [31, 32].…”

Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factors and Binding Proteins in Early Milk from Mothers of Preterm and Term Infants

et al. 2007

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Breast-fed preterm infants often show a better outcome, partly ascribed to the benefit of insulin-like growth factors (IGFs) and their binding proteins (IGFBP). We compared IGF-I, IGF-II, IGFBP-2 and IGFBP-3 levels, measured by radioimmunoassays in milk samples from 30 mothers of preterm (<31 weeks) and from 19 mothers of term (>37 weeks) infants at days 7 and 21 postpartum. Proteolysis of IGFBP-2 within mother’s milk and digestion of ¹²⁵I-IGF-II and ¹²⁵I-IGFBP-2 by gastric juice from neonates were assessed by electrophoretic techniques. Mean concentrations did not differ between preterm and term milk: IGF-I (2.8 ± 0.2 vs. 2.3 ± 0.1 ng/ml), IGF-II (12.0 ± 0.4 vs. 12.2 ± 0.5 ng/ml), IGFBP-3 (100.0 ± 5.1 vs. 80.0 ± 5.8 ng/ml), but did so for IGFBP-2 (3,144 ± 172 vs. 2,428 ± 188 ng/ml, p < 0.02). Immunoblots revealed 42% (p < 0.05) more IGFBP-2 fragments of 14 and 25 kDa in preterm milk. Incubation with gastric juice caused cleavage of ¹²⁵I-IGFBP-2 and partial cleavage of ¹²⁵I-IGF-II. Mutual complexation protected IGF-II and IGFBP-2 from cleavage, suggesting that both are likely to arrive in the bowel in an intact form to exert promotive effects. The results provide further evidence that IGFBP-2 and IGF-II in breast milk are relevant factors for the early development of preterm infants.

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“…In accordance with this hypothesis, individuals born with a birth weight of less than 5.5 lbs [low birth weight (LBW)] are insulin resistant (3,12,15,17,22,28,30,35) and have increased prevalence of type 2 diabetes (10, 15, 28). Additionally, these patients are also prone to exhibit impaired growth in childhood and early adulthood, which may be related to alterations in the growth hormone/IGF-I homeostasis (16,18,20). The mechanisms responsible for these changes associated with LBW are unknown.…”

mentioning

confidence: 99%

Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats

Buhl¹,

Neschen²,

Yonemitsu³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Individuals born with a low birth weight (LBW) have an increased prevalence of type 2 diabetes, but the mechanisms responsible for this association are unknown. Given the important role of insulin resistance in the pathogenesis of type 2 diabetes, we examined insulin sensitivity in a rat model of LBW due to intrauterine fetal stress. During the last 7 days of gestation, rat dams were treated with dexamethasone and insulin sensitivity was assessed in the LBW offspring by a hyperinsulinemic euglycemic clamp. The LBW group had liver-specific insulin resistance associated with increased levels of PEPCK expression. These changes were associated with pituitary hyperplasia of the ACTHsecreting cells, increased morning plasma ACTH concentrations, elevated corticosterone secretion during restraint stress, and an ϳ70% increase in 24-h urine corticosterone excretion. These data support the hypothesis that prenatal stress can result in chronic hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in increased plasma corticosterone concentrations, upregulation of hepatic gluconeogenesis, and hepatic insulin resistance. gluconeogenesis; adrenocorticotropic hormone; corticosterone; type 2 diabetes ACCORDING TO THE BARKER HYPOTHESIS, harmful events taking place during the fetal period can induce life-long changes in different organs predisposing to development of disease (1). In accordance with this hypothesis, individuals born with a birth weight of less than 5.5 lbs [low birth weight (LBW)] are insulin resistant (3,12,15,17,22,28,30,35) and have increased prevalence of type 2 diabetes (10, 15, 28). Additionally, these patients are also prone to exhibit impaired growth in childhood and early adulthood, which may be related to alterations in the growth hormone/IGF-I homeostasis (16,18,20). The mechanisms responsible for these changes associated with LBW are unknown.Recently, fetal stress and high plasma levels of glucocorticoids have been suggested (5, 27) to lead to hypothalamicpituitary-adrenal (HPA) axis hyperactivity, which after birth may result in chronically excessive adrenal glucocorticoid secretion, and an increased risk for the development of type 2 diabetes. However, these findings have been contrasted by other studies that have found no change (32) or decreased HPA axis activity (21) in LBW rat models.To examine the mechanism and potential role of the HPA axis in causing LBW-associated insulin resistance, we assessed insulin-stimulated liver and muscle glucose metabolism, total IGF-I, and IGF-binding proteins (IGFBPs), as well as HPA axis activity in a rat model of stress-induced LBW. MATERIALS AND METHODS Animals.From day 7 of gestation, pregnant female Sprague-Dawley rats (Charles River, Wilmington, MA) were housed singly under temperature (22-23°C)-and light-controlled (12:12-h light-dark cycle) conditions. On day 14 of gestation, rats were randomized into three groups: control, dexamethasone treatment, or foster mother group. From day 14 to day 21 of gestation, a daily subcutaneously injection of d...

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Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein (IGFBP)-3, Phosphoisoforms of IGFBP-1 and Postnatal Growth in Very-Low-Birth-Weight Infants

Cited by 19 publications

References 48 publications

Functional and Complementary Phosphorylation State Attributes of Human Insulin-like Growth Factor-Binding Protein-1 (IGFBP-1) Isoforms Resolved by Free Flow Electrophoresis

Functional and Complementary Phosphorylation State Attributes of Human Insulin-like Growth Factor-Binding Protein-1 (IGFBP-1) Isoforms Resolved by Free Flow Electrophoresis

Insulin-Like Growth Factors and Binding Proteins in Early Milk from Mothers of Preterm and Term Infants

Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats

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