LEUCINE METABOLISM IN LACTATING AND DRY GOATS - EFFECT OF INSULIN ANDSUBSTRATE AVAILABILITY

Early lactating goats show insulin resistance with respect to extramam mary glucose utilization. However, much less is known about the two ma jor factors, insulin and plasma amino acid concentration, that regulat e protein metabolism in lactating goats. To examine this question, the in vivo effect of acute insulin was studied in goats during early lac tation (12-31 days postpartum), midlactation (98-143 days postpartum), and the dry period (approximately 1 yr postpartum). Insulin was infus ed (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 maintai n this condition under insulin treatment. Leucine kinetics were assess ed using a primed continous infusion of L-[1-C-14]-leucine, which star ted 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 hyperaminoacide mic conditions. Thus, in goat as well as humans, infusion of insulin f ails to stimulate protein synthesis even when combined with a substant ially increased provision of amino acids. In contrast, insulin treatme nts caused a dose-dependent inhibition of the endogenous leucine appea rance (an estimate of whole body protein degradation). Under euaminoac idemia the initial slope from the plot of the endogenous leucine appea rance as a function of plasma insulin (an insulin sensitivity index) w as steeper during early lactation than when compared with the dry peri od. A similar trend occurred during midlactation but not to any signif icant degree. These differences were abolished under hyperaminoacidemi a. It was concluded that the ability of physiological insulin to inhib it protein degradation was improved during lactation, demonstrating a clear-cut dissociation between the effects of insulin on protein and g lucose metabolism. This adaptation no doubt may provide a mechanism to save body protein.