Effect of insulin‐like growth factor‐I during the early postnatal period in intrauterine growth‐restricted rats

Ikeda, Naho; Shoji, Hiromichi; Suganuma, H; Ohkawa, Natsuki; Kantake, Masato; Murano, Yayoi; Sakuraya, Koji; Shimizu, Toshiaki

doi:10.1111/ped.12855

Cited by 5 publications

(4 citation statements)

References 39 publications

(71 reference statements)

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“…Three well-defined rat models of IUGR show impaired pancreatic islet development, establish lasting effects in adults, and have been subjected to experimental perinatal interventions to better define the mechanisms leading to diminished islet development and function. Uterine artery ligation (UAL) at embryonic day (E) 18–19 causes an acute decrease in fetal nutrients and oxygen near term (E22), and results in a 10 to 20% reduction in body weight (Delghingaro-Augusto, et al 2014; Ikeda, et al 2016; Ogata, et al 1986; Siebel, et al 2010; Wigglesworth 1964). Maternal dietary restrictions also are widely utilized in rodents to induced IUGR.…”

Section: Animal Models Of Iugr With β-Cell Dysfunctionmentioning

confidence: 99%

The impact of IUGR on pancreatic islet development and β-cell function

Boehmer

Limesand

Rozance

2017

Journal of Endocrinology

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Placental insufficiency is a primary cause of intrauterine growth restriction (IUGR). IUGR increases the risk of developing type 2 diabetes mellitus (T2DM) throughout life, which indicates that insults from placental insufficiency impair β-cell development during the perinatal period because β-cells have a central role in the regulation of glucose tolerance. The severely IUGR fetal pancreas is characterized by smaller islets, less β-cells, and lower insulin secretion. Because of the important associations among impaired islet growth, β-cell dysfunction, impaired fetal growth, and the propensity for T2DM, significant progress has been made in understanding the pathophysiology of IUGR and programing events in the fetal endocrine pancreas. Animal models of IUGR replicate many of the observations in severe cases of human IUGR and allow us to refine our understanding of the pathophysiology of developmental and functional defects in islet from IUGR fetuses. Almost all models demonstrate a phenotype of progressive loss of β-cell mass and impaired β-cell function. This review will first provide evidence of impaired human islet development and β-cell function associated with IUGR and the impact on glucose homeostasis including the development of glucose intolerance and diabetes in adulthood. We then discuss evidence for the mechanisms regulating β-cell mass and insulin secretion in the IUGR fetus, including the role of hypoxia, catecholamines, nutrients, growth factors, and pancreatic vascularity. We focus on recent evidence from experimental interventions in established models of IUGR to understand better the pathophysiological mechanisms linking placental insufficiency with impaired islet development and β-cell function.

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Section: Animal Models Of Iugr With β-Cell Dysfunctionmentioning

confidence: 99%

The impact of IUGR on pancreatic islet development and β-cell function

Boehmer

Limesand

Rozance

2017

Journal of Endocrinology

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“…In a further rat model of uterine artery ligation, IGF-1 treatment during the early postnatal period saw no effect on body or brain weight, which was associated with an increase in hepatic IGFBP-3 [ 80 ]. Little work has been undertaken in the non-human primate (NHP) model in the context of developmental programming.…”

Section: Animal Models Of Manipulation Of the Gh-igf Axismentioning

confidence: 99%

Manipulation of the Growth Hormone-Insulin-Like Growth Factor (GH-IGF) Axis: A Treatment Strategy to Reverse the Effects of Early Life Developmental Programming

Reynolds

Perry

Vickers

2017

IJMS

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Evidence from human clinical, epidemiological, and experimental animal models has clearly highlighted a link between the early life environment and an increased risk for a range of cardiometabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and overnutrition, spanning exposure windows that cover the period from preconception through to early infancy, clearly highlight an increased risk for a range of disorders in offspring in later life. This process, preferentially termed “developmental programming” as part of the developmental origins of health and disease (DOHaD) framework, leads to phenotypic outcomes in offspring that closely resemble those of individuals with untreated growth hormone (GH) deficiency, including increased adiposity and cardiovascular disorders. As such, the use of GH as a potential intervention strategy to mitigate the effects of developmental malprogramming has received some attention in the DOHaD field. In particular, experimental animal models have shown that early GH treatment in the setting of poor maternal nutrition can partially rescue the programmed phenotype, albeit in a sex-specific manner. Although the mechanisms remain poorly defined, they include changes to endothelial function, an altered inflammasome, changes in adipogenesis and cardiovascular function, neuroendocrine effects, and changes in the epigenetic regulation of gene expression. Similarly, GH treatment to adult offspring, where an adverse metabolic phenotype is already manifest, has shown efficacy in reversing some of the metabolic disorders arising from a poor early life environment. Components of the GH-insulin-like growth factor (IGF)-IGF binding protein (GH-IGF-IGFBP) system, including insulin-like growth factor 1 (IGF-1), have also shown promise in ameliorating programmed metabolic disorders, potentially acting via epigenetic processes including changes in miRNA profiles and altered DNA methylation. However, as with the use of GH in the clinical setting of short stature and GH-deficiency, the benefits of treatment are also, in some cases, associated with potential unwanted side effects that need to be taken into account before effective translation as an intervention modality in the DOHaD context can be undertaken.

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“…Several studies reported various reduced placental flow FGR models primarily using the complete ligation of the bilateral uterine arteries with silk threads [ 16 , 17 , 18 , 19 ]. However, it is suggested that in this ligation model, most of the fetal rats proximal to the ligation site will die, and fetal rats far from the ligation site will not experience FGR because of the blood flow from the bilateral ovarian arteries.…”

Section: Introductionmentioning

confidence: 99%

Skeletal Muscle Insulin Resistance in a Novel Fetal Growth Restriction Model

et al. 2023

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The abnormal fetal environment exerts long-term effects on skeletal muscle, and fetal growth restriction (FGR) is associated with insulin resistance in adulthood. In this study, we examined insulin resistance in early adulthood and insulin signaling in skeletal muscle using a novel FGR rat model. Ameroid constrictors (AC) were placed on the bilateral uterine and ovarian arteries of rats on day 17 of gestation; placebo surgery was performed on the control group. We measured body weight at birth, 4, 8, and 12 weeks of age and performed oral glucose tolerance tests at 8 and 12 weeks. Rats were dissected at 12 weeks of age. We examined the mRNA and protein expression of insulin signaling pathway molecules in skeletal muscle. FGR rats had a significantly lower birth weight than control rats (p = 0.002). At 12 weeks of age, the incremental area under the curve of blood glucose was significantly higher, and GLUT4 mRNA and protein expression in soleus muscle was significantly lower in the FGR group than in the control group. Reduced placental blood flow in the AC-attached FGR group caused insulin resistance and altered insulin signaling in skeletal muscles. Therefore, FGR causes skeletal muscle insulin resistance in early adulthood.

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Effect of insulin‐like growth factor‐I during the early postnatal period in intrauterine growth‐restricted rats

Abstract: No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period.

Cited by 5 publications

References 39 publications

The impact of IUGR on pancreatic islet development and β-cell function

The impact of IUGR on pancreatic islet development and β-cell function

Manipulation of the Growth Hormone-Insulin-Like Growth Factor (GH-IGF) Axis: A Treatment Strategy to Reverse the Effects of Early Life Developmental Programming

Skeletal Muscle Insulin Resistance in a Novel Fetal Growth Restriction Model

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