title: Hyperglucagonemia stimulates phenylalanine oxidation in humans.
abstract: Glucagon stimulates in vitro liver phenylalanine (Phe) degradation, thus inducing net protein catabolism. Whether these effects occur also in vivo in humans is not known. Therefore, we studied the effects of physiological hyperglucagonemia on Phe rate of appearance (Ra), hydroxylation, and oxidation in seven normal volunteers during infusions of somatostatin with replacement doses of insulin and growth hormone. Steady-state Phe kinetics were evaluated using the L-[1-14C]Phe tracer both at the end of a 3-h basal glucagon replacement period (glucagon concentration: 212 +/- 115 ng/l) and after a 3-h hormone infusion at the rate of approximately 3 ng x kg-1 x min-1 (--> 654 +/- 280 ng/l). Hyperglucagonemia did not change plasma Phe concentration and Ra but increased Phe oxidation by approximately 30% (P < 0.01). Oxidation was also increased by approximately 24% (P < 0.01) using plasma [14C]tyrosine (Tyr) specific activity as a precursor pool. Phe hydroxylation to Tyr estimated by assuming a fixed ratio of Tyr to Phe Ra (0.73) did not change. Nonhydroxylated Phe disposal decreased by approximately 6% (P = 0.08). These data show that in humans in the postabsorptive state, hyperglucagonemia, with near maintenance of basal insulin and growth hormone concentrations, stimulates Phe oxidation but not Phe hydroxylation, suggesting a different regulation of these two Phe catabolic steps. Glucagon may also reduce Phe availability for protein synthesis.
authors.affiliation: Department of Metabolic Diseases, University of Padova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Tessari
authors.forename: S
authors.initials: S
authors.lastname: Inchiostro
authors.forename: R
authors.initials: R
authors.lastname: Barazzoni
authors.forename: M
authors.initials: M
authors.lastname: Zanetti
authors.forename: M
authors.initials: M
authors.lastname: Vettore
authors.forename: G
authors.initials: G
authors.lastname: Biolo
authors.forename: E
authors.initials: E
authors.lastname: Iori
authors.forename: E
authors.initials: E
authors.lastname: Kiwanuka
authors.forename: A
authors.initials: A
authors.lastname: Tiengo
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology*; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010649:Phenylalanine / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D007328:Insulin; D014443:Tyrosine; D010649:Phenylalanine; D013004:Somatostatin; D013006:Growth Hormone; D005934:Glucagon; D007930:Leucine