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Am J Physiol. 1997 Jan;272(1 Pt 1):E107-17.

Leucine metabolism in chronically hypoglycemic hypoinsulinemic growth-restricted fetal sheep.

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1
Division of Perinatal Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.

Abstract

We measured leucine flux rates during infusions of L-[1-14C]- and L-[1-1C]leucine in fetal sheep exposed to maternal insulin-induced hypoglycemia over the last 8 wk (40%) of gestation to determine effects of chronic glucose deficiency and hypoglycemia on fetal leucine metabolism. Compared with control fetuses (C, n = 5), hypoglycemic fetuses (HG, n = 8) weighed less (C, 3.43 +/- 0.07 kg; HG, 2.32 +/- 0.24 kg), had lower plasma glucose (C, 1.04 +/- 0.02 mM; HG, 0.59 +/- 0.01 mM), insulin (C, 48 +/- 6 pM; HG, 12 +/- 6 pM), and leucine concentrations (C, 195.6 +/- 8.3 microM; HG, 140.8 +/- 15.0 microM), lower rates of net leucine uptake (C, 4.2 +/- 0.6 mumol.min-1.kg-1; HG, 2.1 +/- 0.4 mumol.min-1.kg-1) and leucine flux into protein accretion (C, 2.8 +/- 0.2 mumol.min-1.kg-1; HG, 0.6 +/- 0.1 mumol.min-1.kg-1), and an increased rate of leucine release from protein breakdown (C, 1.1 +/- 0.1 mumol.min-1.kg-1; HG, 3.3 +/- 0.2 mumol.min-1.kg-1) (P < 0.05 for all). Plasma leucine disposal, flux into protein synthesis, and oxidation were not different between groups. We conclude that adaptations of fetal leucine metabolism to long-term hypoglycemia and decreased glucose apply represent diminished leucine uptake and increased leucine release from protein breakdown, which are associated with decreased incorporation of leucine into protein accretion and a slower rate of fetal growth.

[Indexed for MEDLINE]

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