Insulin action upon sugar permeability has been examined in rat diaphragm muscle prepared so that the fibers are either intact or cut. In intact preparations, sucrose and mannitol are largely excluded from the intracellular water while D-galactose, D-xylose, and L-xylose equilibrate in a small fraction of the total cell water; the availability of cell water for D-galactose, D-xylose, and L-xylose is increased by insulin. In cut preparations, in which the cell membrane is not intact, all the sugars studied penetrate into the cell, but intracellular water is not uniformly available for subsequent permeation. Sucrose distributes in a volume of about 40 to 45 per cent of the available cell water; D-xylose, D-galactose, L-xylose, and mannitol are distributed in all or most of the cell water, but these sugars diffuse at different rates. In cut preparations insulin increases the rate of equilibration of D-galactose and D-xylose without significant effect on the other sugars studied; insulin also exerts a "directive" influence on glycogen synthesis from glucose, which cannot be explained solely in terms of accelerated sugar penetration. The significance of these observations in elucidating the locus of insulin action is discussed.

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