The objective of this proposal is to study the adaptations of protein metabolism to the restriction of dietary protein in patients with insulin- dependent diabetes mellitus (IDDM). Balancing their usefulness in forestalling progression of nephropathy, protein restricted diets induce loss of muscle strength and increased adiposity in patients with IDDM. The first major aim of this proposal is to examine whether amino acid redistribution among body proteins occurs during adaptation to protein restriction in IDDM patients. Furthermore, the plan to examine the effect of glycemic control on the metabolic adaptation. Specifically, possible reductions in skeletal muscle myofibrillar protein and albumin synthesis in favor of catabolism-mediating muscle proteins such as ubiquitin- associated proteasomes and acute phase reactant proteins such as fibrinogen will be investigated. The second major aim is to investigate whether the response of protein synthesis rates of specific groups of skeletal muscle proteins to dietary protein restriction and altered glycemic control results, at least in part, from altered expression of genes encoding proteins within these groups. Fractional synthesis rates of soluble proteasome and myofibrillar skeletal muscle proteins, albumin, and fibrinogen will be determined from the incorporation of L-[l-13C]-leucine into the representative proteins or protein complexes. Gene expression of muscle proteins will be estimated by measuring the abundance of myosin heavy chain and proteasome CD protein mRNA. These studies will help identify ways in which limited amino acid resources are reallocated among proteins during dietary protein restriction. They will highlight the influence of commonly experienced perturbations in glycemic control among IDDM patients on these processes and the potential for undernutrition in these patients when they are prescribed protein-restricted diets.
| Brodsky, Irwin G; Suzara, Dennis; Hornberger, Troy A et al. (2004) Isoenergetic dietary protein restriction decreases myosin heavy chain IIx fraction and myosin heavy chain production in humans. J Nutr 134:328-34 |
| Brodsky, Irwin G; Suzara, Dennis; Furman, Mikhail et al. (2004) Proteasome production in human muscle during nutritional inhibition of myofibrillar protein degradation. Metabolism 53:340-7 |
