Leucine metabolism in chronically hypoglycemic, hypoinsulinemic
growth restricted fetal sheep.
Carver, Thomas D., Allen A. Quick, Cecelia C. Teng, Adrian W. Pike,
Paul V. Fennessey, William W. Hay, Jr.
Division of Perinatal Medicine and the Mass Spectrometry Facility,
University of Colorado Health Sciences Center, Denver, Colorado and
the Department of Pediatrics, Madigan Army Medical Center, Tacoma,
Washington
APStracts 3:0185E, 1996.
We measured leucine flux rates during infusions of L-[1-14C] and L-[1
-13C] leucine in fetal sheep exposed to maternal insulin-induced
hypoglycemia over the last 8 weeks (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 (kg: C, 3.43+/-0.07; HG,
2.32+/-0.24), had lower plasma glucose (mM: C, 1.04+/-0.02; HG,
0.59+/-0.01), insulin (pM: C, 48+/-6; HG, 12+/-6), and leucine
concentrations (:M: C, 195.6+/-8.3; HG 140.8+/-15.0), lower rates
(:mol/min/kg) of net leucine uptake (C, 4.2+/-0.6; HG, 2.1+/-0.4) and
leucine flux into protein accretion (C, 2.8+/-0.2; HG 0.6+/-0.1), and
an increased rate of leucine release from protein breakdown (C,
1.1+/-0.1; HG 3.3+/-0.2) (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
supply 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.
Received 12 February 1996; accepted in final form 19 August 1996.
APS Manuscript Number E80-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996