EFFECT OF NONWORKING HETEROTOPIC TRANSPLANTATION ON RAT-HEART GLYCOGEN-METABOLISM

To determine whether the contractile work history of cardiac muscle in fluences its responsiveness to insulin, we examined the effect of insu lin infusion on glycogen metabolism in the rat heart 1 wk after transp lantation into a nonworking heterotopic infrarenal position. Nonworkin g heterografts had higher basal glycogen concentrations than did in si tu working hearts of the same animals (29.9 +/- 2.7 vs. 23.3 +/- 0.8 m u mol/g; P < 0.05), and a smaller fraction of their glycogen synthase enzyme activity was in the physiologically active glycogen synthase I form (8 +/- 2 vs. 22 +/- 3%; P < 0.02). During a 25-min infusion of in sulin (1 U/min) and glucose (30 mg.kg(-1).min(-1)), the fractional gly cogen synthase I activity of heterografts remained lower than that of in situ hearts (29 +/- 5 vs. 56 +/- 7%; P < 0.02) and heterografts syn thesized glycogen more slowly (0.126 +/- 0.07 vs. 0.352 +/- 0.06 mu mo l.g(-1).min(-1); P < 0.02). These effects could be duplicated by a 24- h fast, which similarly increased myocardial glycogen concentration (t o 32. 9 +/- 5.6 mu mol/g). These observations suggest that the perform ance of repetitive contractile work is necessary to maintain the myoca rdium maximally responsive to insulin. Mechanical unloading increases myocardial glycogen concentration, thereby reducing the magnitude of i nsulin's stimulation of glycogen synthase and consequently