Influence of insulin and substrate concentration on protein synthetic rate in fetal tissues

Horn, J. L. Van; Stern, Martin; Young, Maureen; Noakes, D.E.

doi:10.1016/s0034-5288(18)32199-4

Cited by 16 publications

(7 citation statements)

References 15 publications

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“…In contrast to the finding on proteolysis, insulin decreased the rate of protein synthesis seen in fasting lambs, both for the whole body and for the hind-limb muscle. This is in contrast with findings in fasted Reeds et al 1985) and diabetic (Albertese et al 1979;Pain et al 1983) rats, but consistent with observations of decreased rates of muscle-protein synthesis in the fetal lamb (Horn et al 1983) and diabetic man (Nair & Halliday, 1985). Horn et al (19831, however, did observe that in the presence of additional amino acids, insulin would stimulate protein synthesis in the muscle of fetal lambs.…”

Section: Efect Of Insulinsupporting

confidence: 83%

Effect of insulin on hind-limb and whole-body leucine and protein metabolism in fed and fasted lambs

et al. 1987

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1. A combination of isotope-dilution and arterio-venous difference techniques was used to determine rates of leucine metabolism and protein synthesis and degradation in a hind-limb preparation (predominantly muscle) and the whole body of eight lambs fed on milk to appetite and eight lambs fasted from 24 to 48 h.2. Compared with fed lambs, fasted lambs showed decreased rates of protein synthesis in both whole body and hind-limb, and in hind-limb muscle, elevated rates of protein degradation.3. The effects of two rates of insulin infusion on whole-body and hind-limb-muscle leucine metabolism, and in turn on protein metabolism, were determined. Insulin had no significant effect on leucine flux or oxidation (and hence protein synthesis and degradation) in whole-body or hind-limb muscle of fed lambs. In fasted lambs insulin progressively reduced arterial leucine concentration and whole-body leucine flux and oxidation, indicating a reduction in both protein synthesis and degradation. Insulin reduced the rate of leucine efflux from hind-limb muscle, which was followed by a reduction in leucine uptake. Insulin increased hind-limb-muscle glucose uptake in both fed and fasted lambs.4 On the basis that hind-limb muscle was representative of skeletal muscle in general, we estimated that muscle accounted for the same percentage (about 27) of whole-body protein synthesis in both fed and fasted lambs. This percentage was unaffected by infusion of insulin, although the absolute rates differed in fed and fasted lambs.

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Section: Efect Of Insulinsupporting

confidence: 83%

Effect of insulin on hind-limb and whole-body leucine and protein metabolism in fed and fasted lambs

et al. 1987

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“…In addition, it is an important anticatabolic hormone and inhibits gluconeogenesis and proteolysis in the adult (11,17). In the fetal lamb, there is evidence that insulin may enhance net protein accretion more by inhibition of protein degradative processes than by specifically stimulating protein synthesis (18). This mechanism appears similar to results of studies obtained in fetal rats after maternal starvation (19) or in adult animals after STZinduced diabetes (20).…”

Section: Discussionmentioning

confidence: 66%

Effects of Fetal Insulin Deficiency on Growth in Fetal Lambs

et al. 1991

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Insulin may be an important regulator of growth in late fetal life. To assess the importance of endogenous insulin release in regulation of normal fetal growth, eight fetal lamb pairs were given either an intravenous injection of streptozocin (STZ), a nitrosourea that selectively damages pancreatic beta-cells, or buffer infusion (controls). In six preparations, twins were used, and in two cases, triplets, thus allowing for comparison between treated and control fetuses residing in the same intrauterine environment. Fetal STZ injection was associated with relative fetal hyperglycemia, hypoinsulinemia, and a decrease in the fetal plasma insulin-glucose ratio. Fetal lambs exposed to STZ also developed a mild nonprogressive metabolic acidosis compared with controls. Fetal body weight was depressed by 21% overall, the magnitude of reduction related to length of time in utero after STZ injection. Similar reductions in organ weights (liver, heart, and kidney) were also observed in STZ-administered fetuses compared with controls. Protein accretion in carcass, liver, and kidney after STZ was also depressed, but no significant changes in fetal lipid accretion were observed. Skeletal growth, as measured by tail and tibial lengths, was also depressed after STZ but to a lesser extent than body weight or protein accretion. Thus, in a stable maternal environment, isolated fetal insulin deficiency is associated with significant retardation of somatic and skeletal growth and protein deposition.

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“…Intravenous infusion of insulin (4 mIU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) increased the protein fractional synthetic rate in the gastrocnemius muscle in mice by 52%; however, there was no significant effect of insulin on the fractional synthetic rate in liver (3). In fetal lambs, when amino acids were infused, hyperinsulinemia enhanced protein synthesis in skeletal muscle, but no effect was observed in liver (21). In 7-day-old piglets, insulin alone was able to stimulate protein synthesis in muscle but not liver (8)(9)(10).…”

Section: Discussionmentioning

confidence: 90%

“…Conversely, only IGF-I infusion increases the amount of eIF4G. Thus insulin and IGF-I, Amino acid and glucose concentrations decrease with insulin or IGF-I infusion because of inhibitory effects of the peptides on protein breakdown (6,13,21,38,48). It has been well documented that amino acids, specifically leucine, and glucose can regulate protein translation initiation (2,55,59).…”

Section: Discussionmentioning

confidence: 99%

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IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus

Shen

Mallon

Boyle

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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The mechanisms by which insulin-like growth factor I (IGF-I) and insulin regulate eukaryotic initiation factor (eIF)4F formation were examined in the ovine fetus. Insulin infusion increased phosphorylation of eIF4E-binding protein (4E-BP1) in muscle and liver. IGF-I infusion did not alter 4E-BP1 phosphorylation in liver. In muscle, IGF-I increased 4E-BP1 phosphorylation by 27%; the percentage in the gamma-form in the IGF-I group was significantly lower than that in the insulin group. In liver, only IGF-I increased eIF4G. Both IGF-I and insulin increased eIF4E. eIF4G binding in muscle, but only insulin decreased the amount of 4E-BP1 associated with eIF4E. In liver, only IGF-I increased eIF4E. eIF4G binding. Insulin increased the phosphorylation of p70 S6 kinase (p70(S6k)) in both muscle and liver and protein kinase B (PKB/Akt) in muscle, two indicative signal proteins in the phosphatidylinositol (PI) 3-kinase pathway. IGF-I increased PKB/Akt phosphorylation in muscle but had no effect on p70(S6k) phosphorylation in muscle or liver. We conclude that insulin and IGF-I modulate eIF4F formation; however, the two hormones have different regulatory mechanisms. Insulin increases phosphorylation of 4E-BP1 and eIF4E. eIF4G binding in muscle, whereas IGF-I regulates eIF4F formation by increasing total eIF4G. Insulin, but not IGF-I, decreased 4E-BP1 content associated with eIF4E. Insulin regulates translation initiation via the PI 3-kinase-p70(S6k) pathway, whereas IGF-I does so mainly via mechanisms independent of the PI 3-kinase-p70(S6k) pathway.

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Influence of insulin and substrate concentration on protein synthetic rate in fetal tissues

Cited by 16 publications

References 15 publications

Effect of insulin on hind-limb and whole-body leucine and protein metabolism in fed and fasted lambs

Effect of insulin on hind-limb and whole-body leucine and protein metabolism in fed and fasted lambs

Effects of Fetal Insulin Deficiency on Growth in Fetal Lambs

IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus

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