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

Jacqueline Wallace, John Milne, Raymond Aitken, William Hay

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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 (H2O)-H-3, 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 mu mol/ml) and insulin (8.5 vs. 16.9 mu U/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 mu mol.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 mu mol.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.

Original languageEnglish
Pages (from-to)E1233-E1241
Number of pages9
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume293
Issue number5
DOIs
Publication statusPublished - Nov 2007

Keywords

  • insulin action
  • glucose tolerance
  • intrauterine growth restriction
  • adolescent pregnancy
  • placenta
  • low-birth-weight
  • fetal-growth
  • glucose transporters
  • insulin sensitivity
  • postnatal nutrition
  • body-composition
  • endocrine status
  • neonatal sheep
  • age children
  • adiposity

Cite this

Sensitivity to metabolic signals in late-gestation growth-restricted fetuses from rapidly growing adolescent sheep. / Wallace, Jacqueline; Milne, John; Aitken, Raymond; Hay, William.

In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 293, No. 5, 11.2007, p. E1233-E1241.

Research output: Contribution to journalArticle

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AU - Wallace, Jacqueline

AU - Milne, John

AU - Aitken, Raymond

AU - Hay, William

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N2 - 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 (H2O)-H-3, 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 mu mol/ml) and insulin (8.5 vs. 16.9 mu U/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 mu mol.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 mu mol.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.

AB - 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 (H2O)-H-3, 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 mu mol/ml) and insulin (8.5 vs. 16.9 mu U/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 mu mol.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 mu mol.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.

KW - insulin action

KW - glucose tolerance

KW - intrauterine growth restriction

KW - adolescent pregnancy

KW - placenta

KW - low-birth-weight

KW - fetal-growth

KW - glucose transporters

KW - insulin sensitivity

KW - postnatal nutrition

KW - body-composition

KW - endocrine status

KW - neonatal sheep

KW - age children

KW - adiposity

U2 - 10.1152/ajpendo.00294.2007

DO - 10.1152/ajpendo.00294.2007

M3 - Article

VL - 293

SP - E1233-E1241

JO - American Journal of Physiology: Endocrinology and Metabolism

JF - American Journal of Physiology: Endocrinology and Metabolism

SN - 0193-1849

IS - 5

ER -