ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2015
Limited capacity for glucose oxidation in fetal sheep with intrauterine growth restriction.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 87 citations in OpenAlex.
- Nutritional restriction during late gestation disrupts placental transcriptional programs related to metabolism, transport, and immune function in a sheep model.BMC genomics · 2026Article
- Fetal nutrient flux and oxidative metabolism during hypoxia: adaptive responses to defend fetal growth.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Article
- Fetal programming under maternal heat stress: a focus on skeletal muscle growth and nutrition in livestock.Journal of developmental origins of health and disease · 2025Review
- Article
- Increasing maternal glucose concentrations is insufficient to restore placental glucose transfer in chorionic somatomammotropin RNA interference pregnancies.American journal of physiology. Endocrinology and metabolism · 2024Article
- Increased hepatic glucose production with lower oxidative metabolism in the growth-restricted fetus.JCI insight · 2024Article
- Effects of foetal size, sex and developmental stage on adaptive transcriptional responses of skeletal muscle to intrauterine growth restriction in pigs.Scientific reports · 2024Article
- Article
- Elevated Norepinephrine Stimulates Adipocyte Hyperplasia in Ovine Fetuses With Placental Insufficiency and IUGR.Endocrinology · 2023Article
- Decreased Pyruvate but Not Fatty Acid Driven Mitochondrial Respiration in Skeletal Muscle of Growth Restricted Fetal Sheep.International journal of molecular sciences · 2023Article
- Molecular Pathways of Altered Brain Development in Fetuses Exposed to Hypoxia.International journal of molecular sciences · 2023Review
- Placental nanoparticle gene therapy normalizes gene expression changes in the fetal liver associated with fetal growth restriction in a fetal sex-specific manner.Journal of developmental origins of health and disease · 2023Article
- Adaptive responses in uteroplacental metabolism and fetoplacental nutrient shuttling and sensing during placental insufficiency.American journal of physiology. Endocrinology and metabolism · 2023Article
- Timing of maternal nutrient restriction during mid- to late-gestation influences net umbilical uptake of glucose and amino acids in adolescent sheep.Journal of animal science · 2023Article
- Intrauterine growth restriction in piglets modulates postnatal immune function and hepatic transcriptional responses independently of energy intake.Frontiers in physiology · 2023Article
- Dousing the flame: reviewing the mechanisms of inflammatory programming during stress-induced intrauterine growth restriction and the potential for ω-3 polyunsaturated fatty acid intervention.Frontiers in physiology · 2023Review
- Article
- Prenatal transcript levels and metabolomics analyses reveal metabolic changes associated with intrauterine growth restriction and sex.Open biology · 2022Article
- Article
- Prenatal Oxygen and Glucose Therapy Normalizes Insulin Secretion and Action in Growth-Restricted Fetal Sheep.Endocrinology · 2022Article
6 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
Funding
Abstract
Intrauterine growth-restricted (IUGR) fetal sheep, produced by placental insufficiency, have lower oxygen concentrations, higher lactate concentrations, and increased hepatic glucose production that is resistant to suppression by insulin. We hypothesized that increased lactate production in the IUGR fetus results from reduced glucose oxidation, during basal and maximal insulin-stimulated conditions, and is used to support glucose production. To test this, studies were performed in late-gestation control (CON) and IUGR fetal sheep under basal and hyperinsulinemic-clamp conditions. The basal glucose oxidation rate was similar and increased by 30-40% during insulin clamp in CON and IUGR fetuses (P < 0.005). However, the fraction of glucose oxidized was 15% lower in IUGR fetuses during basal and insulin-clamp periods (P = 0.05). IUGR fetuses also had four-fold higher lactate concentrations (P < 0.001) and lower lactate uptake rates (P < 0.05). In IUGR fetal muscle and liver, mRNA expression of pyruvate dehydrogenase kinase (PDK4), an inhibitor of glucose oxidation, was increased over fourfold. In IUGR fetal liver, but not skeletal muscle, mRNA expression of lactate dehydrogenase A (LDHA) was increased nearly fivefold. Hepatic expression of the gluconeogenic genes, phosphoenolpyruvate carboxykinase (PCK)1, and PCK2, was correlated with expression of PDK4 and LDHA. Collectively, these in vivo and tissue data support limited capacity for glucose oxidation in the IUGR fetus via increased PDK4 in skeletal muscle and liver. We speculate that lactate production also is increased, which may supply carbon for glucose production in the IUGR fetal liver.
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