Insulin stimulation of muscle protein synthesis in obese Zucker rats is not via a rapamycin-sensitive pathway

The obese Zucker rat is resistant to insulin for glucose disposal, but it i s unknown whether this insulin resistance is accompanied by alterations of insulin-mediated muscle protein synthesis. We examined rates of muscle prot ein synthesis either with or without insulin in lean and obese Zucker rats with the use of a bilateral hindlimb preparation. Additional experiments ex amined insulin's effect on protein synthesis with or without rapamycin, an inhibitor of protein synthesis. Protein synthesis in red and white gastrocn emius was stimulated by insulin compared with control (no insulin) in obese (n = 10, P< 0.05) but not in lean (n = 10, P> 0.05) Zucker rats. In white gastrocnemius, rapamycin significantly reduced rates of protein synthesis c ompared with control in lean (n = 6) and obese (n = 6) rats; however, in re d gastrocnemius, the attenuating effect of rapamycin occurred only in obese rats. The addition of insulin to rapamycin resulted in rates of synthesis that were similar to those for rapamycin alone for lean rats and to those f or insulin alone (augmented) for obese rats in both tissues. Our results de monstrate that insulin enhances protein synthesis in muscle that is otherwi se characterized as insulin resistant. Furthermore, rapamycin inhibits prot ein synthesis in muscle of obese Zucker rats; however, stimulation of prote in synthesis by insulin is not via a rapamycin-sensitive pathway.