Abstract
Leucine performs a signaling role to enhance protein synthesis by phosphorylating eukaryotic initiation factor (elF) 4E-binding protein 1 (4E-BP1) and 70-kDa riboso-mal protein S6 kinase (S6K1), two key regulatory proteins involved in the initiation of mRNA translation. The purpose of the current study was to assess whether the phosphorylation of 4E-BP1 and S6K1 was increased in skeletal muscle and liver by an oral administration of Leucine to diabetic rats and to determine the in vivo contribution of insulin to a leucine-dependent induction of 4E-BP 1 and S 6K 1 phosphorylation. Food-deprived (18 h) normal and diabetic rats were orally administered 135mg/ 100g body weight L-leucine and sacrificed at 1 h after administration. Leucine administration resulted in enhanced phosphorylation of 4E-BP 1 and S 6K 1 in skeletal muscle and in liver of nondiabetic rats. The stimulatory action of leucine on the phosphorylation of 4E-BP 1 and S 6K 1 in skeletal muscle was not abolished in rats with streptozotocin-induced diabetes. In contrast, leucine administration did not stimulate the phosphorylation of 4E-BP1 and S6K1 in the liver of diabetic rats. These findings suggest that in skeletal muscle, leucine functions as a nutritional signaling molecule that independently regulates the phosphorylation states of 4E-BP 1 and S6K1. In contrast to skeletal muscle, insulin is essential in mediating the leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation in liver.
