Influence of Polymorphisms in Genes Encoding for Insulin-Like Growth Factor (IGF)-I, Insulin, and IGF-Binding Protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 Levels in Umbilical Cord Plasma

Landmann, Eva; Kollerits, Barbara; Kreuder, Joachim; Blum, Werner; Kronenberg, Florian; Rudloff, Silvia

doi:10.1159/000338783

Cited by 8 publications

(4 citation statements)

References 102 publications

(74 reference statements)

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“…Site-specific increase in IGFBP-1 phosphorylation may limit IGF-I bioavailability, which in turn could contribute to the development of fetal growth restriction [23] and IGFBP-1 protein in the placenta is negatively correlated with parameters of neonatal size [24]. There is also evidence that polymorphisms in the promoter region of IGFBP3 are associated with insulin-like growth factor binding protein (IGFBP)-3 plasma levels in cord blood and in postnatal samples [25]. these adaptations persist into adulthood is largely unknown [26].…”

Section: Introductionmentioning

confidence: 99%

Maternal nutritional history modulates the hepatic IGF–IGFBP axis in adult male rat offspring

et al. 2013

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Alterations in early life nutrition lead to an increased risk of obesity and metabolic syndrome in offspring. We have shown that both relative maternal undernutrition (UN) and maternal obesity result in metabolic derangements in offspring, independent of the postnatal dietary environment. Since insulin-like growth factor binding protein 2 (IGFBP2) has been shown to be independently associated with obesity and diabetes risk, we examined the IGF-IGFBP axis in male rat offspring following either maternal UN or maternal obesity to explain possible common pathways in the development of metabolic disorders. Wistar rats were time-mated and fed either a control diet (CONT), 50 % of CONT (UN) or a high-fat (HF) diet throughout pregnancy. Male offspring were weaned onto a standard chow diet and blood and tissues were collected at postnatal day 160. Plasma and hepatic tissue samples were analysed for key players in the IGF-IGFBP system. Both maternal UN and HF resulted in increased fat mass, hyperinsulinemia, hyperleptinemia and altered blood lipid profiles in offspring compared to CONT. Circulating IGF-1 and IGFBP3 levels and hepatic mRNA expression of IGFBP1 and IGFBP2 were significantly decreased in UN and HF offspring compared to CONT. DNA methylation of the IGFBP2 promotor region was similar between maternal dietary groups. Although chaperone gene heat-shock protein 90 and hepatic IGFBP1 were significantly correlated in CONT offspring this effect was absent in both UN and HF offspring. In conclusion, this study is one of the first to directly compare two experimental models of developmental programming representing both ends of the maternal dietary spectrum. Our data suggest that two disparate nutritional models that elicit similar adverse metabolic phenotypes in offspring are characterised by common alterations in the IGF-IGFBP pathway.

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Section: Introductionmentioning

confidence: 99%

Maternal nutritional history modulates the hepatic IGF–IGFBP axis in adult male rat offspring

et al. 2013

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“…Consistently, children with pan-hypopituitarism are not SGA and have no growth failure in the first months of life but frequently are hypoglycemic with low IGF1 levels ( 35 ). Conversely, children with defects in IGF1 signalization are SGA ( 36 ), and many polymorphisms in IGF1 and IGF1R genes have been described associated with FGR ( 37 , 38 ). This dissociation in the role of GH and IGF1 in fetal growth suggests that IGF1 secretion is partially independent of GH during this period.…”

Section: Discussionmentioning

confidence: 99%

Small for Gestational Age Preterm Neonates Exhibit Defective GH/IGF1 Signaling Pathway

Motte-Signoret¹,

Shankar-Aguilera²,

Brailly-Tabard³

et al. 2021

Front. Pediatr.

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Objective: To investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates.Methods: We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60.Results: One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml).Conclusions: SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population.

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“…Variations in IGF axis biomarker concentrations result from a variety of potential factors, such as heritable polymorphisms and ethnicity (17, 18). In pregnancy, insufficient maternal micronutrient intake (particularly iron and calcium) has been associated with reduced fetal IGF-I concentrations (11, 19).…”

Section: Introductionmentioning

confidence: 99%

Prenatal vitamin D and cord blood insulin-like growth factors in Dhaka, Bangladesh

Bilic

Qamar

Onoyovwi

et al. 2019

Endocrine Connections

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Fetal growth restriction is linked to adverse health outcomes and is prevalent in low- and middle-income countries; however, determinants of fetal growth are still poorly understood. The objectives were to determine the effect of prenatal vitamin D supplementation on the insulin-like growth factor (IGF) axis at birth, to compare the concentrations of IGF-I in newborns in Bangladesh to a European reference population and to estimate the associations between IGF protein concentrations and birth size. In a randomized controlled trial in Dhaka, Bangladesh, pregnant women enrolled at 17–24 weeks of gestation were assigned to weekly oral vitamin D3 supplementation from enrolment to delivery at doses of 4200 IU/week, 16,800 IU/week, 28,000 IU/week or placebo. In this sub-study, 559 woman–infant pairs were included for analysis and cord blood IGF protein concentrations were quantified at birth. There were no significant effects of vitamin D supplementation on cord blood concentrations of IGF-I (P = 0.398), IGF-II (P = 0.525), binding proteins (BPs) IGFBP-1 (P = 0.170), IGFBP-3 (P = 0.203) or the molar ratio of IGF-I/IGFBP-3 (P = 0.941). In comparison to a European reference population, 6% of girls and 23% of boys had IGF-I concentrations below the 2.5th percentile of the reference population. IGF-I, IGF-II, IGFBP-3 and the IGF-I/IGFBP-3 ratio were positively associated with at least one anthropometric parameter, whereas IGFBP-1 was negatively associated with birth anthropometry. In conclusion, prenatal vitamin D supplementation does not alter or enhance fetal IGF pathways.

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Influence of Polymorphisms in Genes Encoding for Insulin-Like Growth Factor (IGF)-I, Insulin, and IGF-Binding Protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 Levels in Umbilical Cord Plasma

Cited by 8 publications

References 102 publications

Maternal nutritional history modulates the hepatic IGF–IGFBP axis in adult male rat offspring

Maternal nutritional history modulates the hepatic IGF–IGFBP axis in adult male rat offspring

Small for Gestational Age Preterm Neonates Exhibit Defective GH/IGF1 Signaling Pathway

Prenatal vitamin D and cord blood insulin-like growth factors in Dhaka, Bangladesh

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