AJP - Endocrinology and Metabolism, Vol 272, Issue 1 E107-E117, Copyright © 1997 by American Physiological Society
Leucine metabolism in chronically hypoglycemic hypoinsulinemic growth-restricted fetal sheep
T. D. Carver, A. A. Quick, C. C. Teng, A. W. Pike, P. V. Fennessey and W. W. Hay Jr
Division of Perinatal Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
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.
