Response of leucine metabolism to hyperinsulinemia under amino acid replacement in experimental hyperthyroidism.
We investigated the responsiveness of protein metabolism to insulin as a mediator of the protein catabolic response to hyperthyroidism in humans. Six healthy volunteers were studied in a postabsorptive state before and after oral intake of thyroid hormones (2 micrograms.kg-1.day-1 L-thyroxine for 6 wk along with 1 microgram.kg-1.day-1 triiodothyronine for the last 2 wk). Insulin was infused at 7.14 nmol.kg-1.min-1 for 140 min under euglycemic and eukalemic clamps. An appropriate amino acid infusion was used to blunt insulin-induced hypoaminoacidemia. Leucine kinetics were assessed using a primed continuous infusion of L-[1-13C]leucine. Hyperthyroidism induced a significant increase (P < 0.05) in leucine endogenous appearance rate (a reflection of proteolysis; 2.15 +/- 0.06 vs. 1.76 +/- 0.03 mumol.kg-1.min-1 in the control state), oxidation (0.54 +/- 0.04 vs. 0.47 +/- 0.07), and nonoxidative disposal (a reflection of protein synthesis; 1.80 +/- 0.06 vs. 1.45 +/- 0.06). Insulin lowered proteolysis. Further hyperthyroidism improved the ability of insulin to inhibit proteolysis, whether considered as an absolute decrease (-0.57 +/- 0.02 vs. -0.45 +/- 0.05 mumol.kg-1.min-1, P < 0.05) or related to insulinemia [1.59 +/- 0.11 vs. 1.01 +/- 0.08 mumol leucine.kg-1.min-1/(nmol insulin/l), P < 0.05]. Insulin also moderately (but significantly P < 0.05) lowered protein synthesis in both control and hyperthyroid states. These changes in insulin action may provide a mechanism to save body protein during hyperthyroidism.
Tauveron
I
I
Laboratoire d'Etude du Métabolisme Azoté, Institut National de la Recherche Agronomique, Centre de Clermont-Ferrand, Saint-Genès Champanelle, France.
Charrier
S
S
Champredon
C
C
Bonnet
Y
Y
Berry
C
C
Bayle
G
G
Prugnaud
J
J
Obled
C
C
Grizard
J
J
Thiéblot
P
P
D000328:Adult; D000596:Amino Acids / Q000097:blood / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D002245:Carbon Dioxide; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D006980:Hyperthyroidism / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007651:Keto Acids / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000097:blood / Q000378:metabolism*; D008297:Male; D012016:Reference Values; D012119:Respiration
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D007651:Keto Acids; D002245:Carbon Dioxide; C013082:alpha-ketoisocaproic acid; D007930:Leucine