5B-4 Neonatal Exendin-4 administration normalizes epigenetic modifications of the proximal promoter of Pdx-1

Pinney, Sara E.; Niu, Hongshun; Li, F.; Simmons, Rebecca A.

doi:10.1016/s0378-3782(07)70136-6

Cited by 2 publications

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“…In the restricted placental growth model of IUGR, a 6‐day neonatal course of exendin‐4 prevented the development of diabetes in the placentally restricted rat and normalised glucose tolerance after birth and into adulthood 183 . beta cell mass and PDX‐1 expression were also normalized and remarkably, this effect of neonatal exendin‐4 also restored the epigenetic state of the PDX‐1 promoter to control levels 184 . The fetal rat pancreas, however, unlike the human and sheep, does not develop insulin‐containing cells until the second half of gestation, and pancreatic remodeling with peaks in replication and apoptosis occur in the early postnatal period at 1–2 weeks of age 185,186 .…”

Section: Intervention Strategiesmentioning

confidence: 93%

Early life nutrition and metabolic programming

Fernandez‐Twinn

Ozanne

2010

Annals of the New York Academy of Sciences

151

120

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Research investigating the early programming of adult metabolic disease has in recent years provided much mechanistic insight into how the early environment impacts on long-term health. It includes studies addressing the roles of intrauterine nutrient availability, which is determined by maternal nutrition, maternal exposure to oxygen, toxic events, and infection; the placental interface; and also the early postnatal environment. This review will explore the epidemiological evidence for programming of metabolic disease and provide an overview of the various studies using animals to model metabolic phenotypic outcome. It will also discuss evidence for the proposed molecular mechanisms and the potential for intervention.

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Section: Intervention Strategiesmentioning

confidence: 93%

Early life nutrition and metabolic programming

Fernandez‐Twinn

Ozanne

2010

Annals of the New York Academy of Sciences

151

120

View full text Add to dashboard Cite

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“…This occurs in conjunction with normalisation of β-cell mass and Pdx-1 expression [62]. We have published our preliminary data showing that this induction of Pdx-1 by neonatal exendin-4 also normalises the epigenetic state of the Pdx-1 promoter, probably allowing postnatal expression to be maintained at control levels [63]. In our recent studies in the twin IUGR lamb, neonatal exendin-4 treatment from 1 to 16 days after birth (1 nmol kg −1 d −1 ) reduced fat deposition and growth during treatment [64], similar to responses in neonatal PR rats and in diabetic humans [60,62].…”

Section: Future Directions: Interventions To Restore Insulin Actiomentioning

confidence: 99%

Review: Placental Programming of Postnatal Diabetes and Impaired Insulin Action after IUGR

et al. 2010

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Being born small due to poor growth before birth increases the risk of developing metabolic disease, including type 2 diabetes, in later life. Inadequate insulin secretion and decreasing insulin sensitivity contribute to this increased diabetes risk. Impaired placental growth, development and function are major causes of impaired fetal growth and development and therefore of IUGR. Restricted placental growth (PR) and function in non-human animals induces similar changes in insulin secretion and sensitivity as in human IUGR, making these valuable tools to investigate the underlying mechanisms and to test interventions to prevent or ameliorate the risk of disease after IUGR. Epigenetic changes induced by an adverse fetal environment are strongly implicated as causes of later impaired insulin action. These have been well-characterised in the PR rat, where impaired insulin secretion is linked to epigenetic changes at the Pdx-1 promotor and reduced expression of this transcription factor. Present research is particularly focussed on developing intervention strategies to prevent or reverse epigenetic changes, and normalise gene expression and insulin action after PR, in order to translate this to treatments to improve outcomes in human IUGR.

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5B-4 Neonatal Exendin-4 administration normalizes epigenetic modifications of the proximal promoter of Pdx-1

Cited by 2 publications

References 0 publications

Early life nutrition and metabolic programming

Early life nutrition and metabolic programming

Review: Placental Programming of Postnatal Diabetes and Impaired Insulin Action after IUGR

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