Regulation of postnatal pancreatic Pdx1 and downstream target genes after gestational exposure to protein restriction in rats

Abuzgaia, Awatif M.; Hardy, Daniel B.; Arany, Edith

doi:10.1530/rep-14-0245

Cited by 20 publications

(14 citation statements)

References 52 publications

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“…Importantly, when PI-IUGR fetuses were infused chronically with a complete mixture of amino acids enriched in the BCAAs, not only did islet size increase, but islet vascularity increased in proportion to the increase in islet size (Brown et al 2016). Similar results occurred in the LP fetal rat, where gestational taurine supplementation prevented the decrease in fetal islet vascularity and VEGFA expression, and the increase in islet cell apoptosis (Abuzgaia et al 2015). These were associated with higher β-cell mass in taurine supplemented LP fetal rats compared to non-supplemented LP fetal rats although insulin secretion was not enhanced (Boujendar et al 2003; Boujendar et al 2002).…”

Section: Pancreatic Developmentsupporting

confidence: 67%

“…Lower insulin secretion, smaller islets, lower islet density, less β-cells, and decreased pancreatic weight and insulin content are hallmarks of the IUGR fetal pancreas in the various animal models (Abuzgaia, et al 2015; Green et al 2010). Defects in β-cell replication and expression of genes regulating β-cell proliferation, apoptosis, and neogenesis all contribute to reduced β-cell mass to varying extents in the different models.…”

Section: Pancreatic Developmentmentioning

confidence: 99%

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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: Pancreatic Developmentsupporting

confidence: 67%

Section: Pancreatic Developmentmentioning

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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“…We chose to look at epigenetic changes in the promotor region of the PDX1 gene because of its ubiquity in β cell development and insulin production (33). Also, manipulation of the protein content in the postnatal diet in rodents has been found to alter both PDX1 expression and activation (34). The increased insulin mRNA expression that we found in supplemented female lambs is consistent with the decreased repressor marks and increased activator marks observed.…”

Section: Articlessupporting

confidence: 64%

Brief neonatal nutritional supplementation has sex-specific effects on glucose tolerance and insulin regulating genes in juvenile lambs

et al. 2016

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“…). PDX1 regulates the expression of the insulin, GLUT2 and GCK genes, influencing glucose homeostasis (Abuzgaia, ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, pancreatic duodenal homeobox-1 (PDX1) is involved in the initial development of the pancreas, in the differentiation of β-cells and in maintaining this tissue throughout life (Jonsson et al 1994). PDX1 regulates the expression of the insulin, GLUT2 and GCK genes, influencing glucose homeostasis (Abuzgaia, 2015).…”

Section: Introductionmentioning

confidence: 99%

Early weaning induces short‐ and long‐term effects on pancreatic islets in Wistar rats of both sexes

Pietrobon

Miranda

Bertasso

et al. 2020

The Journal of Physiology

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Key points The World Health Organization recommends exclusive breastfeeding until 6 months of age as an important strategy to reduce child morbidity and mortality. Studies have associated early weaning with the development of obesity and type 2 diabetes in adulthood. In our model, we demonstrated that early weaning leads to increased insulin secretion in adolescent males and reduced insulin secretion in adult offspring. Early weaned males exhibit insulin resistance in skeletal muscle. Early weaning did not change insulin signalling in the muscle of female offspring. Taking into account that insulin resistance is one of the primary factors for the development of type 2 diabetes mellitus, this work demonstrates the importance of breastfeeding in the fight against this disease. Abstract Early weaning (EW) leads to short‐ and long‐term obesity and diabetes. This phenotype is also observed in experimental models, in which early‐weaned males exhibit abnormal insulinaemia in adulthood. However, studies regarding the effect of EW on pancreatic islets are rare. We investigated the mechanisms by which glycaemic homeostasis is altered in EW models through evaluations of insulin secretion and its signalling pathway in offspring. Lactating Wistar rats and their pups were divided into the following groups: non‐pharmacological EW (NPEW): mothers were wrapped with an adhesive bandage on the last 3 days of lactation; pharmacological EW (PEW): mothers received bromocriptine to inhibit prolactin (1 mg/kg body mass/day) on the last 3 days of lactation; and control (C): pups underwent standard weaning at PN21. Offspring of both sexes were euthanized at PN45 and PN180. At PN45, EW males showed higher insulin secretion (vs. C). At PN170, PEW males exhibited hyperglycaemia in an oral glucose tolerance test (vs. C and NPEW). At PN180, EW male offspring were heavier; however, both sexes showed higher visceral fat. Insulin secretion was lower in EW offspring of both sexes. Males from both EW groups had lower glucokinase in islets, but unexpectedly, PEW males showed higher GLUT2, than did C. EW males exhibited lower insulin signalling in muscle. EW females exhibited no changes in these parameters compared with C. We demonstrated distinct alterations in the insulin secretion of EW rats at different ages. Despite the sex dimorphism in insulin secretion in adolescence, both sexes showed impaired insulin secretion in adulthood due to EW.

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Regulation of postnatal pancreatic Pdx1 and downstream target genes after gestational exposure to protein restriction in rats

Cited by 20 publications

References 52 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

Brief neonatal nutritional supplementation has sex-specific effects on glucose tolerance and insulin regulating genes in juvenile lambs

Early weaning induces short‐ and long‐term effects on pancreatic islets in Wistar rats of both sexes

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