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Increased insulin sensitivity and maintenance of glucose utilization rates in fetal sheep with placental insufficiency and intrauterine growth restriction.
Am J Physiol Endocrinol Metab. 2007 Dec; 293(6):E1716-25.AJ

Abstract

In this study we determined body weight-specific fetal (umbilical) glucose uptake (UGU), utilization (GUR), and production rates (GPR) and insulin action in intrauterine growth-restricted (IUGR) fetal sheep. During basal conditions, UGU from the placenta was 33% lower in IUGR fetuses, but GUR was not different between IUGR and control fetuses. The difference between glucose utilization and UGU rates in the IUGR fetuses demonstrated the presence and rate of fetal GPR (41% of GUR). The mRNA concentrations of the gluconeogenic enzymes glucose-6-phophatase and PEPCK were higher in the livers of IUGR fetuses, perhaps in response to CREB activation, as phosphorylated CREB/total CREB was increased 4.2-fold. A hyperglycemic clamp resulted in similar rates of glucose uptake and utilization in IUGR and control fetuses. The nearly identical GURs in IUGR and control fetuses at both basal and high glucose concentrations occurred at mean plasma insulin concentrations in the IUGR fetuses that were approximately 70% lower than controls, indicating increased insulin sensitivity. Furthermore, under basal conditions, hepatic glycogen content was similar, skeletal muscle glycogen was increased 2.2-fold, the fraction of fetal GUR that was oxidized was 32% lower, and GLUT1 and GLUT4 concentrations in liver and skeletal muscle were the same in IUGR fetuses compared with controls. These results indicate that insulin-responsive fetal tissues (liver and skeletal muscle) adapt to the hypoglycemic-hypoinsulinemic IUGR environment with mechanisms that promote glucose utilization, particularly for glucose storage, including increased insulin action, glucose production, shunting of glucose utilization to glycogen production, and maintenance of glucose transporter concentrations.

Authors+Show Affiliations

Department of Pediatrics, University of Colorado Health Sciences Center, Aurora, Colorado, USA. Limesand@Ag.Arizona.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17895285

Citation

Limesand, Sean W., et al. "Increased Insulin Sensitivity and Maintenance of Glucose Utilization Rates in Fetal Sheep With Placental Insufficiency and Intrauterine Growth Restriction." American Journal of Physiology. Endocrinology and Metabolism, vol. 293, no. 6, 2007, pp. E1716-25.
Limesand SW, Rozance PJ, Smith D, et al. Increased insulin sensitivity and maintenance of glucose utilization rates in fetal sheep with placental insufficiency and intrauterine growth restriction. Am J Physiol Endocrinol Metab. 2007;293(6):E1716-25.
Limesand, S. W., Rozance, P. J., Smith, D., & Hay, W. W. (2007). Increased insulin sensitivity and maintenance of glucose utilization rates in fetal sheep with placental insufficiency and intrauterine growth restriction. American Journal of Physiology. Endocrinology and Metabolism, 293(6), E1716-25.
Limesand SW, et al. Increased Insulin Sensitivity and Maintenance of Glucose Utilization Rates in Fetal Sheep With Placental Insufficiency and Intrauterine Growth Restriction. Am J Physiol Endocrinol Metab. 2007;293(6):E1716-25. PubMed PMID: 17895285.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased insulin sensitivity and maintenance of glucose utilization rates in fetal sheep with placental insufficiency and intrauterine growth restriction. AU - Limesand,Sean W, AU - Rozance,Paul J, AU - Smith,Danielle, AU - Hay,William W,Jr Y1 - 2007/09/25/ PY - 2007/9/27/pubmed PY - 2008/2/26/medline PY - 2007/9/27/entrez SP - E1716 EP - 25 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 293 IS - 6 N2 - In this study we determined body weight-specific fetal (umbilical) glucose uptake (UGU), utilization (GUR), and production rates (GPR) and insulin action in intrauterine growth-restricted (IUGR) fetal sheep. During basal conditions, UGU from the placenta was 33% lower in IUGR fetuses, but GUR was not different between IUGR and control fetuses. The difference between glucose utilization and UGU rates in the IUGR fetuses demonstrated the presence and rate of fetal GPR (41% of GUR). The mRNA concentrations of the gluconeogenic enzymes glucose-6-phophatase and PEPCK were higher in the livers of IUGR fetuses, perhaps in response to CREB activation, as phosphorylated CREB/total CREB was increased 4.2-fold. A hyperglycemic clamp resulted in similar rates of glucose uptake and utilization in IUGR and control fetuses. The nearly identical GURs in IUGR and control fetuses at both basal and high glucose concentrations occurred at mean plasma insulin concentrations in the IUGR fetuses that were approximately 70% lower than controls, indicating increased insulin sensitivity. Furthermore, under basal conditions, hepatic glycogen content was similar, skeletal muscle glycogen was increased 2.2-fold, the fraction of fetal GUR that was oxidized was 32% lower, and GLUT1 and GLUT4 concentrations in liver and skeletal muscle were the same in IUGR fetuses compared with controls. These results indicate that insulin-responsive fetal tissues (liver and skeletal muscle) adapt to the hypoglycemic-hypoinsulinemic IUGR environment with mechanisms that promote glucose utilization, particularly for glucose storage, including increased insulin action, glucose production, shunting of glucose utilization to glycogen production, and maintenance of glucose transporter concentrations. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/17895285/Increased_insulin_sensitivity_and_maintenance_of_glucose_utilization_rates_in_fetal_sheep_with_placental_insufficiency_and_intrauterine_growth_restriction_ L2 - http://journals.physiology.org/doi/full/10.1152/ajpendo.00459.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -