Altered gas exchange, limited glucose and branched chain amino acids, and hypoinsulinism retard fetal growth in the rat

Ogata, Edward S.; Bussey, Mary E.; Finley, Sandra

doi:10.1016/0026-0495(86)90064-8

Cited by 164 publications

(128 citation statements)

References 33 publications

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“…This model does not completely restrict blood supply to the fetus, but reduces it adequately to reflect human uteroplacental insufficiency, which can be caused by preeclampsia, maternal smoking and abnormalities in placental development. These neonatal IUGR rats demonstrated reduced glucose, insulin, insulin-like growth factor 1, amino acid and oxygen concentrations (69)(70)(71) . These IUGR animals later developed age-associated diabetes (72) .…”

Section: Uterine Placental Ligationmentioning

confidence: 94%

The impact of early nutrition on the ageing trajectory

Tarry-Adkins

Ozanne

2014

Proc. Nutr. Soc.

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Epidemiological studies, including those in identical twins, and in individuals in utero during periods of famine have provided robust evidence of strong correlations between low birthweight and subsequent risk of disease in later life, including type 2 diabetes (T2D), CVD, and metabolic syndrome. These and studies in animal models have suggested that the early environment, especially early nutrition, plays an important role in mediating these associations. The concept of early life programming is therefore widely accepted; however the molecular mechanisms by which early environmental insults can have long-term effects on a cell and consequently the metabolism of an organism in later life, are relatively unclear. So far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification and microRNA) and permanent changes in cellular ageing. Many of the conditions associated with early-life nutrition are also those which have an age-associated aetiology. Recently, a common molecular mechanism in animal models of developmental programming and epidemiological studies has been development of oxidative stress and macromolecule damage, specifically DNA damage and telomere shortening. These are phenotypes common to accelerated cellular ageing. Thus, this review will encompass epidemiological and animal models of developmental programming with specific emphasis on cellular ageing and how these could lead to potential therapeutic interventions and strategies which could combat the burden of common age-associated disease, such as T2D and CVD.

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Section: Uterine Placental Ligationmentioning

confidence: 94%

The impact of early nutrition on the ageing trajectory

Tarry-Adkins

Ozanne

2014

Proc. Nutr. Soc.

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“…Growth retarded fetal rats have critical features of a metabolic profile characteristic of growth retarded human fetuses: decreased levels of glucose, insulin, insulin-like-growth factor 1 (IGF-I), amino acids, and oxygen (50)(51)(52). By 6 months of age, IUGR rats develop diabetes with a phenotype remarkably similar to that observed in the human with type 2 diabetes: progressive dysfunction in insulin secretion and insulin action.…”

Section: What Animal Models Can Tell Usmentioning

confidence: 99%

Developmental origins of diabetes: The role of oxidative stress

Simmons

2006

Free Radical Biology and Medicine

121

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The 'thrifty phenotype' hypothesis proposes that the fetus adapts to an adverse intrauterine milieu by optimizing the use of a reduced nutrient supply to ensure survival, but by favoring the development of certain organs over that of others, this leads to persistent alterations in the growth and function of developing tissues. This concept has been somewhat controversial, however recent epidemiological, clinical, and animal studies provide support for the developmental origins of disease hypothesis. Underlying mechanisms include reprogramming of the hypothalamicpituitary-adrenal axis, islet development, and insulin signaling pathways. Emerging data suggests that oxidative stress and mitochondrial dysfunction may also play a critical role in the pathogenesis of type 2 diabetes in individuals who were growth retarded at birth.

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“…Uteroplacental insufficiency limits the availability of substrates, growth factors, and hormones to the fetus and retards growth during gestation. This abnormal intrauterine milieu modifies gene expression in pluripotential and terminally differentiated cells resulting in permanent structural and functional changes in key organs such as the pancreas, liver, and muscle (13)(14)(15)(16)(17). We have developed a rat model of uteroplacental insufficiency, hereafter designated as IUGR for intra-uterine growth retardation induced by bilateral uterine artery ligation at 19 days of gestation (term is 22 days).…”

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confidence: 99%

Neonatal Exendin-4 Prevents the Development of Diabetes in the Intrauterine Growth Retarded Rat

Stoffers

Desai²,

León³

et al. 2003

Diabetes

248

207

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Uteroplacental insufficiency resulting in fetal growth retardation is a common complication of pregnancy and a significant cause of perinatal morbidity and mortality. Epidemiological studies show an increased incidence of type 2 diabetes in humans who were growth retarded at birth. The mechanisms by which an abnormal intrauterine milieu leads to the development of diabetes in adulthood are not known. Therefore, a rat model of uteroplacental insufficiency was developed; intrauterine growth-retarded (IUGR) rats develop diabetes with a phenotype similar to that observed in the human with type 2 diabetes. We show here that administration of a pancreatic ␤-cell trophic factor, exendin-4 (Ex-4), during the prediabetic neonatal period dramatically prevents the development of diabetes in this model. This occurs because neonatal Ex-4 prevents the progressive reduction in insulin-producing ␤-cell mass that is observed in IUGR rats over time. Expression of PDX, a critical regulator of pancreas development and islet differentiation, is restored to normal levels, and islet ␤-cell proliferation rates are normalized by the neonatal Ex-4 treatment. These results indicate that exposure to Ex-4 in the newborn period reverses the adverse consequences of fetal programming and prevents the development of diabetes in adulthood. Diabetes 52: 734 -740, 2003

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Altered gas exchange, limited glucose and branched chain amino acids, and hypoinsulinism retard fetal growth in the rat

Cited by 164 publications

References 33 publications

The impact of early nutrition on the ageing trajectory

The impact of early nutrition on the ageing trajectory

Developmental origins of diabetes: The role of oxidative stress

Neonatal Exendin-4 Prevents the Development of Diabetes in the Intrauterine Growth Retarded Rat

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