Muscle Protein Turnover in the Perfused Hindquarters of Lean and Genetically Obese-Diabetic (db/db) Mice

The stability of the perfused mouse hindquarter was assessed for a period of 5 h, and the preparation shown to remain stable for metabolic studies over this time period. Muscle protein synthesis and degradation rates in lean and diabetic-obese (db/db) mice were measured using the in situ perfused hindquarter preparation. The rates of protein synthesis were 48% lower in the muscles of intact db/db mice than in the lean controls when expressed per gram TCA precipitable protein and 46% lower when expressed per gram dry weight. Adrenalectomy, which has been shown to restore the lean body mass of the db/db mice to normal, had the effect of returning protein synthesis rate in muscle of db/db mice to lean control values. Insulin at a dose of 1 mU/ml stimulated protein synthesis in lean mice only, showing that the process of protein synthesis in the db/db mice is also insensitive to insulin. Measurements of the rates of degradation of muscle protein showed no differences between lean and db/db mice. These findings suggest that the decreased lean body mass of db/db mice is the result of a defect in protein synthesis rather than due to altered degradation.