Response of leucine metabolism to hyperinsulinemia under amino acid replacement in experimental hyperthyroidism

Abstract

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.

Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown

“…This is in keeping with the notion that thyroid hormones have both anabolic and catabolic actions, as suggested by the reports of Rochon et al (29) and Tauveron et al (35) using a leucine tracer method. At the whole body level, we observed a 40% increase in protein synthesis rate (calculated as total phenylalanine flux Ϫ phenylalanine-to-tyrosine degrada- Data are presented as means Ϯ SE.…”

“…Studies of protein metabolism in hyperthyroid patients before and after treatment have suggested that the net protein catabolism is mainly because of depressed rates of whole body protein synthesis (7,20) with low or normal rates of proteolysis. In experimental hyperthyroidism, increased rates of proteolysis with no change in protein synthesis rates have been reported (6,16), whereas Tauveron et al (35) found both increased proteolysis and synthesis. Thyroid hormones have both anabolic and catabolic effects; therefore, the net effect on protein metabolism may vary, and the above inconsistencies may relate to heterogeneity both of the hyperthyroid subjects, in terms of severity and duration of hyperthyroidism, and of the methods employed.…”

Whole body leucine flux in HIV-infected patients treated with or without protease inhibitors

“…However, in a previous study, we showed that a similar amino acid-glucose infusion, albeit in the presence of insulin, did not stimulate the nonoxidative leucine disposal in healthy subjects. As was observed in the PIϪ group in the present study, amino acid-glucose infusion also impaired nonoxidative leucine disposal (Ϫ10%) (41). Moreover, Giordano et al (14) clearly showed that amino acid infusion, which increased plasma amino acids by 1.25-1.50 above baseline (as in the present study), did not change nonoxidative leucine disposal in healthy volunteers.…”

“…Total whole body leucine turnover rate (Q, mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was determined using the equation (28,25,41,43,44)…”

Effect of medroxyprogesterone acetate on the efficiency of an oral protein-rich nutritional support in HIV-infected patients

“…Similar effects were recorded in normal volunteers and dysthyroid patients when glucose and amino acids were given along with insulin [27,28]. Indeed insulin is known to mediate the decrease in proteolysis.…”