Response of leucine metabolism to hyperinsulinemia under amino acid
replacement in experimental hyperthyroidism.
Tauveron, Igor, Sophie Charrier*, Claude Champredon, Yves Bonnet,
Christiane Berry, Gerard Bayle, Jacques Prugnaud, Christiane Obled,
Jean Grizard, and Philippe Thieblot.
Laboratoire d'Etude du M[acute]etabolisme Azot[acute]e, Institut
National de la Recherche Agronomique, Centre de Clermont-Ferrand,
Centre de Recherche en Nutrition Humaine d'Auvergne, 63122 Saint
-Gen[grave]es Champanelle and Service d'Endocrinologie et Maladies
M[acute]etaboliques CHU de Clermont-Ferrand, B.P. 69, 63003 Clermont
-Ferrand cedex, France
APStracts 2:0078E, 1995.
We investigated the responsiveness of protein metabolism to insulin as
a mediator of the protein catabolic response to hyperthyroidism in
man. Six healthy volunteers were studied in a postabsorptive state
before and after oral intake of thyroid hormones (2 [mu]g.kg-1.day-1
L-T4 for 6 weeks along with 1 [mu]g.kg-1.day-1 T3 on the last two
weeks). Insulin was infused at 7.14 nmol.kg-1.min-1 for 140 min under
euglycemic and eukaliemic 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 [mu]mol.kg-1.min-1 in Control state),
oxidation (0.54 +/- 0.04 vs 0.47 +/- 0.07), and non oxidative
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
[mu]mol.kg-1.min-1, p<0.05) or related to insulinemia (1.59 +/-
0.11 vs 1.01 +/- 0.08 [mu]mol leucine.kg-1.min-1/ nmol insulin.l-1,
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.
Received 2 December 1994; accepted in final form 6 April 1995.
APS Manuscript Number E509-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.