OBJECTIVE: The authors determined the effect of laparoscopic cholecystectomy on protein synthesis in skeletal muscle. In addition to a decrease in muscle protein synthesis, after open cholecystectomy, the authors previously demonstrated a decrease in insulin sensitivity. This study on patients undergoing laparoscopic and open surgery, therefore, included simultaneous measurements of protein synthesis and insulin sensitivity. SUMMARY BACKGROUND DATA: Laparoscopy has become a routine technique for several operations because of postoperative benefits that allow rapid recovery. However, its effect on postoperative protein catabolism has not been characterized. Conventional laparotomy induces a drop in muscle protein synthesis, whereas degradation is unaffected. METHODS: Patients were randomized to laparoscopic or open cholecystectomy, and the rate of protein synthesis in skeletal muscle was determined 24 hours postoperatively by the flooding technique using L-(2H5)phenylalanine, during a hyperinsulinemic normoglycemic clamp to assess insulin sensitivity. RESULTS: The protein synthesis rate decreased by 28% (1.77 +/- 0.11%/day vs. 1.26 +/- 0.08%/day, p < 0.01) in the laparoscopic group and by 20% (1.97 +/- 0.15%/day vs. 1.57 +/- 0.15%/day, p < 0.01) in the open cholecystectomy group. In contrast, the fall in insulin sensitivity after surgery was lower with laparoscopic (22 +/- 2%) compared with open surgery (49 +/- 5%). CONCLUSIONS: Laparoscopic cholecystectomy did not avoid a substantial decline in muscle protein synthesis, despite improved insulin sensitivity. The change in the two parameters occurred independently, indicating different mechanisms controlling insulin sensitivity and muscle protein synthesis.