Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia.

Autor:	Houin SS; Perinatal Research Center, Department of Pediatrics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado., Rozance PJ; Perinatal Research Center, Department of Pediatrics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado., Brown LD; Perinatal Research Center, Department of Pediatrics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado., Hay WW Jr; Perinatal Research Center, Department of Pediatrics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado., Wilkening RB; Perinatal Research Center, Department of Pediatrics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado., Thorn SR; Perinatal Research Center, Department of Pediatrics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado stephanie.thorn@ucdenver.edu.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2015 Feb 15; Vol. 308 (4), pp. E306-14. Date of Electronic Publication: 2014 Dec 16.
DOI:	10.1152/ajpendo.00396.2014
Abstrakt:	Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 (P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-¹³C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 (P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia (P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia. (Copyright © 2015 the American Physiological Society.)
Databáze:	MEDLINE
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