Effect of glucose supply on ovine uteroplacental  glucose metabolism

Aldoretta, Peter W.; Hay, William W.

doi:10.1152/ajpregu.1999.277.4.r947

Cited by 25 publications

(28 citation statements)

References 18 publications

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“…In fetal sheep, β-cell responsiveness to glucose develops during the second half of gestation, paralleling the fetal glucose responsiveness observed in human pregnancies (Aldoretta and Hay 1999; Molina, et al 1993; Nicolini et al 1990). Due to the accessibility of the fetal vasculature for chronic catheterization, sheep models of placental insufficiency and IUGR allow for testing mechanisms that link in utero conditions of IUGR, impaired islet development and β-cell dysfunction.…”

Section: Animal Models Of Iugr With β-Cell Dysfunctionmentioning

confidence: 60%

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: 60%

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

Boehmer

Limesand

Rozance

2017

Journal of Endocrinology

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“…Fructose and lactate, another by-product of glucose metabolism by the placental tissue, are of significance to the total conceptus and placental oxidative metabolism (McGowan et al 1995). Aldoretta and Hay (1999) demonstrated in sheep that the rate at which the placental tissue synthesizes fructose seems to depend directly on the placental glucose supply. As placental mass and SA become significantly larger in IVP concepti, more placental glucose utilization or transport may occur in IVP concepti.…”

Section: Discussionmentioning

confidence: 99%

“…Fructose, the predominant reducing sugar present in foetal plasma and foetal fluids in cattle (Goodwin 1956, Hugget & Nixon 1961, Nixon 1963, is transported in mammalian cells by Glut-5 and supposedly by other novel members of the glucose transporter family (Girniene et al 2003). The placental fructogenic activity appears to be dependent on glucose supply to the uteroplacental tissue (Aldoretta & Hay 1999), but evidence demonstrating the importance of fructose transporters at the bovine placenta is lacking.…”

Section: Introductionmentioning

confidence: 99%

Evidence of increased substrate availability to in vitro-derived bovine foetuses and association with accelerated conceptus growth

Bertolini

Moyer²,

Mason³

et al. 2004

Reproduction

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Changes in placental development have been associated with foetal abnormalities after in vitro embryo manipulations. This study was designed to investigate bovine conceptus development and substrate levels in plasma and fluids in in vivo-and in vitro-produced (IVP) concepti and neonates. In vivo-produced and IVP embryos were derived by established embryo production procedures. Pregnant animals from both groups were slaughtered on days 90 or 180 of gestation, or allowed to go to term. Conceptus and neonatal physical traits were recorded; foetal, maternal and neonatal blood, and foetal fluids were collected for the determination of blood and fluid chemistry, and glucose, fructose and lactate concentrations. Placental transcripts for specific glucose transporters were determined by quantitative RT-PCR. No significant differences in uterine and conceptus traits were observed between groups on day 90. On day 180, larger uterine, placental and foetal weights, and an increase in placental gross surface area (SA) in IVP pregnancies were associated with increased glucose and fructose accumulation in foetal plasma and associated fluids, with no differences in the expression of components of the glucose transporter system. Therefore, the enlarged placental SA in IVP pregnancies suggests an increase in substrate uptake and transport capacity. Newborn IVP calves displayed higher birth weights and plasma fructose concentrations soon after birth, findings which appeared to be associated with clinical and metabolic distress. Our results indicated larger concepti and increased placental fructogenic capacity in mid-to late IVP pregnancies, features which appeared to be associated with an enhanced substrate supply, potentially glucose, to the conceptus.

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“…). In sheep and other species, about half of the glucose taken up by the gravid uterus is used by the uteroplacental tissues for both oxidative and non‐oxidative metabolism, including glycolysis (Aldoretta & Hay, ; Fowden et al . ).…”

Section: Introductionmentioning

confidence: 99%

“…The net amount of glucose reaching the fetus also depends on the rate of glucose consumption by the uteroplacental tissues for their own metabolic activities (Hay et al 1990). In sheep and other species, about half of the glucose taken up by the gravid uterus is used by the uteroplacental tissues for both oxidative and non-oxidative metabolism, including glycolysis (Aldoretta & Hay, 1999;Fowden et al 2001). The lactate produced glycolytically is then released into both maternal and fetal circulations (Sparks et al 1982).…”

Section: Introductionmentioning

confidence: 99%

A physiological increase in maternal cortisol alters uteroplacental metabolism in the pregnant ewe

Vaughan

Davies

Ward

et al. 2016

The Journal of Physiology

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Key points Fetal nutrient supply is dependent, in part, upon the transport capacity and metabolism of the placenta.The stress hormone, cortisol, alters metabolism in the adult and fetus but it is not known whether cortisol in the pregnant mother affects metabolism of the placenta.In this study, when cortisol concentrations were raised in pregnant sheep by infusion, proportionately more of the glucose taken up by the uterus was consumed by the uteroplacental tissues while less was transferred to the fetus, despite an increased placental glucose transport capacity. Concomitantly, the uteroplacental tissues produced lactate at a greater rate.The results show that maternal cortisol concentrations regulate uteroplacental glycolytic metabolism, producing lactate for use in utero.Prolonged increases in placental lactate production induced by cortisol overexposure may contribute to the adverse effects of maternal stress on fetal wellbeing. AbstractFetal nutrition is determined by maternal availability, placental transport and uteroplacental metabolism of carbohydrates. Cortisol affects maternal and fetal metabolism, but whether maternal cortisol concentrations within the physiological range regulate uteroplacental carbohydrate metabolism remains unknown. This study determined the effect of maternal cortisol infusion (1.2 mg kg−1 day−1 i.v. for 5 days, n = 20) on fetal glucose, lactate and oxygen supplies in pregnant ewes on day ∼130 of pregnancy (term = 145 days). Compared to saline infusion (n = 21), cortisol infusion increased maternal, but not fetal, plasma cortisol (P < 0.05). Cortisol infusion also raised maternal insulin, glucose and lactate concentrations, and blood pH, PnormalCO2 and HCO3 − concentration. Although total uterine glucose uptake determined by Fick's principle was unaffected, a greater proportion was consumed by the uteroplacental tissues, so net fetal glucose uptake was 29% lower in cortisol‐infused than control ewes (P < 0.05). Concomitantly, uteroplacental lactate production was > 2‐fold greater in cortisol‐ than saline‐treated ewes (P < 0.05), although uteroplacental O2 consumption was unaffected by maternal treatment. Materno‐fetal clearance of non‐metabolizable [3H]methyl‐d‐glucose and placental SLC2A8 (glucose transporter 8) gene expression were also greater with cortisol treatment. Fetal plasma glucose, lactate or α‐amino nitrogen concentrations were unaffected by treatment although fetal plasma fructose and hepatic lactate dehydrogenase activity were greater in cortisol‐ than saline‐treated ewes (P < 0.05). Fetal plasma insulin levels and body weight were also unaffected by maternal treatment. During stress, cortisol‐dependent regulation of uteroplacental glycolysis may allow increased maternal control over fetal nutrition and metabolism. However, when maternal cortisol concentrations are raised chronically, prolonged elevation of uteroplacental lactate production may compromise fetal wellbeing.

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Effect of glucose supply on ovine uteroplacental glucose metabolism

Cited by 25 publications

References 18 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

Evidence of increased substrate availability to in vitro-derived bovine foetuses and association with accelerated conceptus growth

A physiological increase in maternal cortisol alters uteroplacental metabolism in the pregnant ewe

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