title: Effect of hyperinsulinemia on amino acid utilization and oxidation independent of glucose metabolism in the ovine fetus.
abstract: We studied the effect of acute hyperinsulinemia on amino acid (AA) utilization and oxidation rates independent of insulin-enhanced glucose metabolism in fetal sheep. Metabolic studies were conducted in each fetus (n = 11) under three experimental periods. After control period (C) study, a fetal hyperinsulinemic-euglycemic-euaminoacidemic (HI-euG-euAA) clamp was established, followed by a hyperinsulinemic-hypoglycemic-euaminoacidemic (HI-hypoG-euAA) clamp to decrease glucose metabolic rates toward C values. Infusions of (3)H(2)0, L-[1-(13)C]leucine, and [(14)C(U)]glucose were administered to measure blood flow, leucine oxidation, and fetal glucose uptake, utilization, and oxidation in each period. Fetal glucose utilization rate increased 1.7-fold with hyperinsulinemia (C 5.8 +/- 0.8 mg.kg(-1).min(-1), HI-euG-euAA 10 +/- 1.3 mg.kg(-1).min(-1), P < 0.0001), returning to rates not different from C with hypoglycemia (HI-hypoG-euAA 7.1 +/- 0.9 mg.kg(-1).min(-1) vs. C value, P = 0.15). Fetal glucose oxidation rate increased 1.7-fold with hyperinsulinemia (C 3.1 +/- 0.2 mg.kg(-1).min(-1), HI-euG-euAA 5.4 +/- 0.4 mg.kg(-1).min(-1), P < 0.0001) and decreased to near control rates with hypoglycemia (4.0 +/- 0.3 HI-hypoG-euAA vs. C value, P = 0.006). AA utilization rates increased with hyperinsulinemia for all essential and most nonessential AAs (P < 0.001) and did not change when insulin-induced increases in glucose utilization returned to control rates. Leucine oxidation rate increased 1.7-fold with hyperinsulinemia (C 1.0 +/- 0.3 micromol.min(-1).kg(-1), HI-euG-euAA 1.7 +/- 0.3 micromol.min(-1).kg(-1), P < 0.002) and did not change when glucose oxidation rate was decreased with hypoglycemia. These results demonstrate that, in fetal sheep, insulin promotes AA utilization and oxidation independent of its simultaneous effects on glucose metabolism. In acute hyperinsulinemic conditions, AA oxidation does not change when insulin-induced glucose utilization is prevented.
authors.affiliation: Department of Pediatrics, University of Colorado Health Sciences Center, Aurora, CO 80045, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Brown
authors.forename: William W
authors.initials: WW
authors.lastname: Hay
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000097:blood; D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood; D007930:Leucine / Q000378:metabolism; D010084:Oxidation-Reduction; D011247:Pregnancy; D012756:Sheep
chemical_list: D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D007328:Insulin; D019344:Lactic Acid; D007930:Leucine; D005947:Glucose