Dose-response relationship for a positive inotropic effect of insulin on isolated papillary muscle

Beneficial effect of glucose and insulin on the myocardium are still a matter of discussion. The influence of insulin on isometric force of contraction of right ventricular papillary muscles of guinea pigs was studied. The papillary muscles were mounted vertically in a 95% O2, 5% CO2 modified Krebs-Hensuleit solution (31.5 degrees C, 5.5 mM glucose) and stimulated l/s. A positive inotropic effect of insulin was dedectable at a concentration of 5 x 10(-4) IU/ml insulin, was half maximal (52% above controle force of contraction) at 8 x 10(-3) IU/ml and maximal at 10(-1) IU/ml. The maximal positive inotropic effect was observed 4.7 +/- 0.6 min after addition of insulin. After the maximum there was a decrease to a steady state level of 109.8 +/- 8.5% of control (p less than 0.05) in 14.6 +/- 1.3 min. Higher glucose (16.5 mM) only shifted the half maximal positive inotropic effect to 5.5 x 10(-3) IU/ml insulin (n.s.). Inhibition of glycolysis with hypoxia or jodoacetate (5 x 10(-5) M) did not prevent the positive inotropic effect as known as 75% of control force was retained. When glucose transport was blocked with phlorizin (5 x 10(-3) M) or phloritin (5 x 10(-4) M) no positive inotropic action of insulin was observed. Therefore we conclude that the positive inotropic effect of insulin in isolated papillary muscles is mediated by inhanced glucose transport.