Leucine metabolism in lactating and dry goats: effect of insulin and substrate availability

Abstract

Early lactating goats show insulin resistance with respect to extramammary glucose utilization. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in lactating goats. To examine this question, the in vivo effect of acute insulin was studied in goats during early lactation (12-31 days postpartum), midlactation (98-143 days postpartum), and the dry period (approximately 1 yr postpartum). Insulin was infused (at 0.36 or 1.79 nmol/min) under euglycemic and eukaliemic clamps. In addition, appropriate amino acid infusion was used to blunt insulin-induced hypoaminoacidemia or to create hyperaminoacidemia and maintain this condition under insulin treatment. Leucine kinetics were assessed using a primed continuous infusion of L-[1-14C]-leucine, which started 2.5 h before insulin. In all animals the insulin treatments failed to stimulate the nonoxidative leucine disposal (an estimate of whole body protein synthesis) under both euaminoacidemic and hyperaminoacidemic conditions. Thus, in goat as well as humans, infusion of insulin fails to stimulate protein synthesis even when combined with a substantially increased provision of amino acids. In contrast, insulin treatments caused a dose-dependent inhibition of the endogenous leucine appearance (an estimate of whole body protein degradation). Under euaminoacidemia the initial slope from the plot of the endogenous leucine appearance as a function of plasma insulin (an insulin sensitivity index) was steeper during early lactation than when compared with the dry period. A similar trend occurred during midlactation but not to any significant degree. These differences were abolished under hyperaminoacidemia. It was concluded that the ability of physiological insulin to inhibit protein degradation was improved during lactation, demonstrating a clear-cut dissociation between the effects of insulin on protein and glucose metabolism. This adaptation no doubt may provide a mechanism to save body protein.

The effect of supplemental propionate on insulin responsiveness to glucose and tissue responsiveness to insulin in relation to feeding in sheep

“…This [13]. Insulin infusion reduces whole body protein degradation and concentrations of plasma free amino acids [7,25]. There [17].…”

Skeletal muscle protein mobilization during the progression of lactation

“…Protein synthesis in skeletal muscle is highly regulated, and a fall in the rate of this process is suggested to contribute to protein mobilization during starvation (24,26) and in lactation (6,8,34,39). However, the regulation of protein catabolism in lactating animals remains unclear, and the participation of skeletal muscle proteolysis is especially poorly understood.…”

Manipulating tissue metabolism by amino acids

“…Protein-deficient diets cause inhibition of protein synthesis, whereas the effect on proteolysis seems to depend on the severity of the deficiency. Hyperaminoacidemia induced by intravenous infusion of amino acids increases muscle protein synthesis, at least when measurements are performed using the constant infusion of labelled amino acids (Watt et al, 1992;Tesseraud et al, 1993). Amino acids are essential for postprandial stimulation of protein synthesis, as demonstrated in the rat (Yoshizawa et al, 1998) and the chicken (Yaman et al, 2000).…”