ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2012
A physiological increase in insulin suppresses gluconeogenic gene activation in fetal sheep with sustained hypoglycemia.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- A Two-Hour Fetal Glucagon Infusion Stimulates Hepatic Catabolism of Amino Acids in Fetal Sheep.International journal of molecular sciences · 2025Article
- Influence of Cold Environments on Growth, Antioxidant Status, Immunity and Expression of Related Genes in Lambs.Animals : an open access journal from MDPI · 2022Article
- MiR-29a Family as a Key Regulator of Skeletal Muscle Dysplasia in a Porcine Model of Intrauterine Growth Retardation.Biomolecules · 2022Article
- Effects of chronic hyperinsulinemia on metabolic pathways and insulin signaling in the fetal liver.American journal of physiology. Endocrinology and metabolism · 2020Article
- Skeletal muscle amino acid uptake is lower and alanine production is greater in late gestation intrauterine growth-restricted fetal sheep hindlimb.American journal of physiology. Regulatory, integrative and comparative physiology · 2019Article
- Sustained hypoxemia in late gestation potentiates hepatic gluconeogenic gene expression but does not activate glucose production in the ovine fetus.American journal of physiology. Endocrinology and metabolism · 2019Article
- Differential effects of intrauterine growth restriction and a hypersinsulinemic-isoglycemic clamp on metabolic pathways and insulin action in the fetal liver.American journal of physiology. Regulatory, integrative and comparative physiology · 2019Article
- Postnatal effects of intrauterine treatment of the growth-restricted ovine fetus with intra-amniotic insulin-like growth factor-1.The Journal of physiology · 2018Article
- The role of fructose‑1,6‑bisphosphatase 1 in abnormal development of ovarian follicles caused by high testosterone concentration.Molecular medicine reports · 2017Article
- Exogenous amino acids suppress glucose oxidation and potentiate hepatic glucose production in late gestation fetal sheep.American journal of physiology. Regulatory, integrative and comparative physiology · 2017Article
- Role of placental insufficiency and intrauterine growth restriction on the activation of fetal hepatic glucose production.Molecular and cellular endocrinology · 2016Article
- Chronic anemic hypoxemia increases plasma glucagon and hepatic PCK1 mRNA in late-gestation fetal sheep.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Limited capacity for glucose oxidation in fetal sheep with intrauterine growth restriction.American journal of physiology. Regulatory, integrative and comparative physiology · 2015Article
- Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia.American journal of physiology. Endocrinology and metabolism · 2015Article
- A physiological increase in insulin suppresses muscle-specific ubiquitin ligase gene activation in fetal sheep with sustained hypoglycemia.Physiological reports · 2014Article
- Changes in fetal mannose and other carbohydrates induced by a maternal insulin infusion in pregnant sheep.Journal of animal science and biotechnology · 2014Article
- Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep.American journal of physiology. Endocrinology and metabolism · 2013Article
- Increased fetal insulin concentrations for one week fail to improve insulin secretion or β-cell mass in fetal sheep with chronically reduced glucose supply.American journal of physiology. Regulatory, integrative and comparative physiology · 2013Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Reduced maternal glucose supply to the fetus and resulting fetal hypoglycemia and hypoinsulinemia activate fetal glucose production as a means to maintain cellular glucose uptake. However, this early activation of fetal glucose production may be accompanied by hepatic insulin resistance. We tested the capacity of a physiological increase in insulin to suppress fetal hepatic gluconeogenic gene activation following sustained hypoglycemia to determine whether hepatic insulin sensitivity is maintained. Control fetuses (CON), hypoglycemic fetuses induced by maternal insulin infusion for 8 wk (HG), and 8 wk HG fetuses that received an isoglycemic insulin infusion for the final 7 days (HG+INS) were studied. Glucose and insulin concentrations were 60% lower in HG compared with CON fetuses. Insulin was 50% higher in HG+INS compared with CON and four-fold higher compared with HG fetuses. Expression of the hepatic gluconeogenic genes, PCK1, G6PC, FBP1, GLUT2, and PGC1A was increased in the HG and reduced in the HG+INS liver. Expression of the insulin-regulated glycolytic and lipogenic genes, PFKL and FAS, was increased in the HG+INS liver. Total FOXO1 protein expression, a gluconeogenic activator, was 60% higher in the HG liver. Despite low glucose, insulin, and IGF1 concentrations, phosphorylation of AKT and ERK was higher in the HG liver. Thus, a physiological increase in fetal insulin is sufficient for suppression of gluconeogenic genes and activation of glycolytic and lipogenic genes in the HG fetal liver. These results demonstrate that fetuses exposed to sustained hypoglycemia have maintained hepatic insulin action in contrast to fetuses exposed to placental insufficiency.
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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.