Effects of insulin on ovine fetal leucine kinetics and protein metabolism.

Milley, J. Ross

doi:10.1172/jci117142

Cited by 38 publications

(23 citation statements)

References 37 publications

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“…Under physiological conditions in mammals, insulin and amino acids have interactive effects on amino acid metabolism. An acute insulin infusion will decrease plasma amino acid concentrations, which then limit the effectiveness of insulin to promote amino acid utilization (30,41). Amino acids stimulate pancreatic insulin secretion, such that some studies of amino acid infusion have not been able to discriminate between insulin-and amino acid-specific effects.…”

Section: Discussionmentioning

confidence: 99%

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Insulin is required for amino acid stimulation of dual pathways for translational control in skeletal muscle in the late-gestation ovine fetus

Brown¹,

Rozance²,

Barry³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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Section: Discussionmentioning

confidence: 99%

“…During late gestation, insulin stimulates amino acid utilization, whole body protein accretion, and skeletal muscle fractional protein synthesis under conditions of amino acid sufficiency (10,30,41,44). The fetus also responds to an amino acid infusion by increasing protein synthesis and accretion (24).…”

mentioning

confidence: 99%

Insulin is required for amino acid stimulation of dual pathways for translational control in skeletal muscle in the late-gestation ovine fetus

Brown¹,

Rozance²,

Barry³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…The circulating plasma insulin concentration in fetal sheep significantly enhances glucose utilization [1], inhibits protein breakdown [2], and promotes fetal growth [3]. Central to these processes are the mechanisms that regulate fetal pancreatic insulin secretion and thereby fetal plasma insulin concentration, especially over the second half of gestation when glucose utilization rate, protein turnover rate, and growth rate in the fetus are very high.…”

Section: Introductionmentioning

confidence: 99%

Maturation of Glucose-Stimulated Insulin Secretion in Fetal Sheep

Aldoretta

Carver

Hay³

1998

Neonatology

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To determine the gestational maturation of fetal insulin response to glucose and arginine and the effects of sustained hyperglycemia on these processes, we measured insulin secretion in different groups of fetal sheep at 75, 100, 122, and 137 days of gestation (50, 67, 81, and 91% of term gestation, respectively). The basal glucose concentration decreased progressively from 1.36 ± 0.16 mM at 75 days to 1.00 ± 0.07 mM at 137 days (p < 0.05). The fetal plasma insulin concentration did not change (54 ± 11 pM at 75 days, 68 ± 8 pM at 137 days), but there was a significant increase in the increment in plasma insulin concentration in response to a hyperglycemic clamp over this same period (ΔI pM/ΔG mM) from 20 ± 3 at 75 days to 105 ± 8 at 137 days (p < 0.001). The ΔI (pM) in response to arginine also increased from 129 ± 17 pM at 75 days to 635 ± 103 pM at 137 days (p < 0.001). Sustained hyperglycemia from 90 to 100 days reduced the ΔI (pM)/ΔG (mM) to glucose (13 ± 2, p < 0.01) and the ΔI pM to arginine (369 ± 86, p < 0.05) to values less than those found in euglycemic animals (ΔI/ΔG = 58 ± 4 to glucose, ΔI = 525 ± 71 to arginine). Thus, glucose and arginine stimulate insulin secretion at midgestation at 20% of the rate near term, and there is a consistently positive developmental pattern of insulin secretion to these secretagogues over the second half of gestation. Furthermore, chronic, high, relatively constant hyperglycemia blunts insulin secretion to glucose and arginine close to midgestation, similar to the effect seen near term. Such developmental and adaptive capacities may account for an important part of the variability in fetal glucose metabolism observed in animal models and human cases of diabetes during pregnancy.

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“…Pharmacological hyperinsulinemia consistently decreases amino acid catabolism and, hence, increases fetal amino acid accretion (36,41). Protein synthesis is generally enhanced, although the statistical power of several studies has not been adequate to prove this definitively.…”

mentioning

confidence: 99%

“…Insulin infusion generally results in a fall of 20-40% in fetal amino acid concentrations (36,41). Infusion of IGF-I also causes amino acid concentrations to fall, although to a lesser extent than does insulin (8,44).…”

mentioning

confidence: 99%

Protein anabolic effects of insulin and IGF-I in the ovine fetus

Shen

Wisniowski

Ahmed

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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We determined the effect of insulin and/or recombinant human (rh)IGF-I infusion on ovine fetal phenylalanine kinetics, protein synthesis, and phenylalanine accretion. The chronically catheterized fetal lamb model was used at 130 days gestation. All studies were performed while fetal glucose and amino acid concentrations were held constant. Experimental infusates were 1) saline, 2) rhIGF-I plus a replacement dose of insulin (40 nmol), 3) insulin (890 mIU/h), and 4) IGF-I plus insulin (40 nmol IGF-I/h and 890 mIU insulin/h). Both hormones increased glucose and amino acid utilization, with insulin having a greater effect. The major effect on phenylalanine kinetics was a pronounced fall in phenylalanine hydroxylation, again with insulin having the greatest effect. Whole body protein breakdown was not significantly altered by either hormone; whole body protein synthesis was significantly increased during the combined infusion. Protein accretion was increased by both hormones, with the greatest increase during combined infusion. The fractional synthetic rate (FSR) of circulating albumin was increased by IGF-I but not by insulin. Both hormones significantly increased skeletal muscle FSR without a synergistic effect. The anabolic effects of insulin and IGF-I were more pronounced in these studies than in previous studies where amino acid concentrations were not maintained. The present data also suggest that insulin and IGF-I promote fetal growth through distinct, organ-specific mechanisms.

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Effects of insulin on ovine fetal leucine kinetics and protein metabolism.

Cited by 38 publications

References 37 publications

Insulin is required for amino acid stimulation of dual pathways for translational control in skeletal muscle in the late-gestation ovine fetus

Insulin is required for amino acid stimulation of dual pathways for translational control in skeletal muscle in the late-gestation ovine fetus

Maturation of Glucose-Stimulated Insulin Secretion in Fetal Sheep

Protein anabolic effects of insulin and IGF-I in the ovine fetus

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