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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/E1233    most recent 00294.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wallace, J. M. Articles by Hay, W. W. Search for Related Content PubMed PubMed Citation Articles by Wallace, J. M. Articles by Hay, W. W., Jr.

Sensitivity to metabolic signals in late-gestation growth-restricted fetuses from rapidly growing adolescent sheep

¹Rowett Research Institute, Bucksburn, Aberdeen, United Kingdom; and ²Perinatal Research Center, University of Colorado Health Sciences Center, Aurora, Colorado

Submitted 15 May 2007 ; accepted in final form 11 August 2007

Fetal sensitivity to insulin and glucose was investigated during fetal hyperinsulinemic-euglycemic (HI-euG, n = 18) and hyperglycemic-euinsulinemic (HG-euI, n = 12) clamps. Singleton bearing adolescent ewes were fed high (H) or control (C) nutrient intakes to induce compromised or normal placental/fetal size, respectively. Catheters were inserted in the umbilical vein (v), fetal artery, (a) and veins, and studies were conducted between day 126 and 133 of gestation. Umbilical blood flow (UmBF) was determined by the steady-state transplacental diffusion technique using ³H₂O, and glucose fluxes were quantified by the Fick principle. For the HI-euG study, fetal glucose utilization was measured at spontaneously occurring fetal insulin concentrations and two additional higher levels, whereas fetal glucose was clamped at the initial baseline level. For the HG-euI study, fetal insulin was suppressed by somatostatin infusion, and fetal glucose utilization was determined at baseline (before somatostatin) glucose concentrations, and at 150 and 200% of this value. Placentome weight (219 vs. 395 g), fetal weight (2,965 vs. 4,373 g), and UmBF (519 vs. 794 ml/min) were lower (P < 0.001) in H than in C groups. Relative to control fetuses, glucose extraction (G[v – a]/G[v] x 100) in the nonperturbed state was higher (21.7 vs. 15.9%) in growth-restricted fetuses despite lower glucose (0.78 vs. 1.05 µmol/ml) and insulin (8.5 vs. 16.9 µU/ml) concentrations (all P < 0.001). During the HI-euG study, total fetal glucose utilization rate increased in response to higher insulin concentrations (65 and 64% in H and C groups). Similarly during the HG-euI study, a twofold increase in glucose supply increased fetal glucose utilization by 41 and 44% in H and C groups, respectively. Throughout both studies, absolute total fetal glucose utilization rates were reduced in H vs. C groups (P < 0.01) but were similar when expressed per kilogram fetus (HI-euG: 34.7, 49.5, and 57.5 in H vs. 34.7, 51.2, and 56.1 µmol·min^–1·kg^–1 in C, HG-euI: 28.7, 35.7, and 40.8 in H vs. 32.9, 34.5, and 43.8 µmol·min^–1·kg^–1 in C). These normal body weight-specific metabolic responses to short-term experimental increases in plasma insulin and glucose in response to chronic IUGR indicate maintained mechanisms of insulin action and glucose uptake/utilization capacity, which, if persistent, might predispose such IUGR offspring to excessive energy deposition in later life.

insulin action; glucose tolerance; intrauterine growth restriction; adolescent pregnancy; placenta