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.
