The effects of glucose and insulin on contraction of the isolated diaphragm

High glucose concentrations (55 mM) were found to suppress the isometric contraction tension of rat diaphragm. The effect appears to be due to the resulting transmembrane osmotic gradient in spite of the fact that glucose uptake by the diaphragm is fairly rapid. Insulin can reverse the effect of hypertonic glucose to a considerable extent. The problems of estimating intracellular glucose concentration in the isolated muscle are considered. Estimates of intracellular glucose taking into account extracellular space and extracellular diffusion gradients were made using a two-compartment model. Calculations based on the model show that in the presence of insulin, intracellular glucose increases from about 1 to 19 mumol/ml of muscle fibre. The mean transmembrane glucose concentration gradient dcreases from 41 to 18 mumol/ml. With the use of the model it appears possible to relate most of the observed effect of glucose and insulin on isometric contraction to their influence on the osmotic gradient across the muscle fibre membrane. Insulin appears to have some additional effects on muscles suppressed by hypertonic solutions which are not accounted for by this mechanism.