title: Leucine metabolism in chronically hypoglycemic hypoinsulinemic growth-restricted fetal sheep.
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.
authors.affiliation: Division of Perinatal Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Carver
authors.forename: A A
authors.initials: AA
authors.lastname: Quick
authors.forename: C C
authors.initials: CC
authors.lastname: Teng
authors.forename: A W
authors.initials: AW
authors.lastname: Pike
authors.forename: P V
authors.initials: PV
authors.lastname: Fennessey
authors.forename: W W
authors.initials: WW
authors.lastname: Hay
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002247:Carbon Isotopes; D002908:Chronic Disease; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005317:Fetal Growth Retardation / Q000097:blood*; D005333:Fetus / Q000033:anatomy & histology; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000097:blood*; D007651:Keto Acids / Q000097:blood; D007930:Leucine / Q000097:blood / Q000378:metabolism*; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D010920:Placenta / Q000033:anatomy & histology; D011247:Pregnancy; D012756:Sheep
chemical_list: D001786:Blood Glucose; D002247:Carbon Isotopes; D007328:Insulin; D007651:Keto Acids; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D010100:Oxygen