ArticleDiabetes2013
Increased hepatic glucose production in fetal sheep with intrauterine growth restriction is not suppressed by insulin.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
68 citing papers in PubMed, 88 citations in OpenAlex.
- Elevated catecholamine derivatives homovanillic acid and vanillylmandelic acid in the plasma and amniotic fluid of growth-restricted fetal sheep.Pediatric research · 2026Article
- Experimental chronic fetal hyperglucagonemia stimulates hepatic pathways for amino acid catabolism and gluconeogenesis.The Journal of endocrinology · 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
- Hypoxic pregnancy promotes fibrosis and increases stress metabolites in the ovine fetal liver.The Journal of physiology · 2025Article
- Medical Nutrition Therapy for Women with Gestational Diabetes: Current Practice and Future Perspectives.Nutrients · 2025Review
- PlacentaAmerican journal of physiology. Endocrinology and metabolism · 2025Article
- A Two-Hour Fetal Glucagon Infusion Stimulates Hepatic Catabolism of Amino Acids in Fetal Sheep.International journal of molecular sciences · 2025Article
- Increased hepatic glucose production with lower oxidative metabolism in the growth-restricted fetus.JCI insight · 2024Article
- Dysfunctional Postnatal Mitochondrial Energy Metabolism in a Patient with Neurodevelopmental Defects Caused by Intrauterine Growth Restriction Due to Idiopathic Placental Insufficiency.International journal of molecular sciences · 2024Article
- Insulin resistance and dyslipidemia in low-birth-weight goat kids.Frontiers in veterinary science · 2024Article
- Four Markers Useful for the Distinction of Intrauterine Growth Restriction in Sheep.Animals : an open access journal from MDPI · 2023Article
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- Adaptive responses in uteroplacental metabolism and fetoplacental nutrient shuttling and sensing during placental insufficiency.American journal of physiology. Endocrinology and metabolism · 2023Article
- 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
- 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
- Prenatal transcript levels and metabolomics analyses reveal metabolic changes associated with intrauterine growth restriction and sex.Open biology · 2022Article
- Prenatal Oxygen and Glucose Therapy Normalizes Insulin Secretion and Action in Growth-Restricted Fetal Sheep.Endocrinology · 2022Article
- Fetal Sex Does Not Impact Placental Blood Flow or Placental Amino Acid Transfer in Late Gestation Pregnant Sheep With or Without Placental Insufficiency.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Intrauterine growth restriction (IUGR) increases the risk for metabolic disease and diabetes, although the developmental origins of this remain unclear. We measured glucose metabolism during basal and insulin clamp periods in a fetal sheep model of placental insufficiency and IUGR. Compared with control fetuses (CON), fetuses with IUGR had increased basal glucose production rates and hepatic PEPCK and glucose-6-phosphatase expression, which were not suppressed by insulin. In contrast, insulin significantly increased peripheral glucose utilization rates in CON and IUGR fetuses. Insulin robustly activated AKT, GSK3β, and forkhead box class O (FOXO)1 in CON and IUGR fetal livers. IUGR livers, however, had increased basal FOXO1 phosphorylation, nuclear FOXO1 expression, and Jun NH(2)-terminal kinase activation during hyperinsulinemia. Expression of peroxisome proliferator-activated receptor γ coactivator 1α and hepatocyte nuclear factor-4α were increased in IUGR livers during basal and insulin periods. Cortisol and norepinephrine concentrations were positively correlated with glucose production rates. Isolated IUGR hepatocytes maintained increased glucose production in culture. In summary, fetal sheep with IUGR have increased hepatic glucose production, which is not suppressed by insulin despite insulin sensitivity for peripheral glucose utilization. These data are consistent with a novel mechanism involving persistent transcriptional activation in the liver that seems to be unique in the fetus with IUGR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.