Evidence for a catabolic role of glucagon during an amino acid load.
Despite the strong association between protein catabolic conditions and hyperglucagonemia, and enhanced glucagon secretion by amino acids (AA), glucagon's effects on protein metabolism remain less clear than on glucose metabolism. To clearly define glucagon's catabolic effect on protein metabolism during AA load, we studied the effects of glucagon on circulating AA and protein dynamics in six healthy subjects. Five protocols were performed in each subject using somatostatin to inhibit the secretion of insulin, glucagon, and growth hormone (GH) and selectively replacing these hormones in different protocols. Total AA concentration was the highest when glucagon, insulin, and GH were low. Selective increase of glucagon levels prevented this increment in AA. Addition of high levels of insulin and GH to high glucagon had no effect on total AA levels, although branched chain AA levels declined. Glucagon mostly decreased glucogenic AA and enhanced glucose production. Endogenous leucine flux, reflecting proteolysis, decreased while leucine oxidation increased in protocols where AA were infused and these changes were unaffected by the hormones. Nonoxidative leucine flux reflecting protein synthesis was stimulated by AA, but high glucagon attenuated this effect. Addition of GH and insulin partially reversed the inhibitory effect of glucagon on protein synthesis. We conclude that glucagon is the pivotal hormone in amino acid disposal during an AA load and, by reducing the availability of AA, glucagon inhibits protein synthesis stimulated by AA. These data provide further support for a catabolic role of glucagon at physiological concentrations.
Charlton
M R
MR
Endocrine Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Adey
D B
DB
Nair
K S
KS
D020155:3-Hydroxybutyric Acid; D000328:Adult; D000596:Amino Acids / Q000097:blood*; D002395:Catecholamines / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000097:blood / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006885:Hydroxybutyrates / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000097:blood; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology
D000596:Amino Acids; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D013004:Somatostatin; D005934:Glucagon; D007930:Leucine; D005947:Glucose; D005990:Glycerol; D020155:3-Hydroxybutyric Acid; D006854:Hydrocortisone