Regulation of glucose uptake in muscle. I. The effects of insulin and anoxia on glucose transport and phosphorylation in the isolated, perfused heart of normal rats.

The stimulation of glucose uptake by muscle cells is recognized as one of the most important and characteristic actions of insulin. This hormone effect was shown in earlier work (1, 2) to be due to an acceleration of glucose transport through the cell membrane, as first proposed by Levine et al. (3, 4). Glucose uptake is also stimulated by anoxia, as recently demonstrated by Randle and Smith (6) who attributed this effect to acceleration of the transport process. Morgan, Randle, and Regen (7) confirmed this conclusion and showed, in addition, that anoxia stimulated glucose phosphorylation. In the present work, we have studied the effects of insulin and anoxia on glucose uptake in more detail and have attempted, in particular, to analyze the kinetics of the uptake process. In this connection, the importance of glucose transport through the membrane as a rate-limiting step for uptake has been appreciated only recently. Furthermore, the specific nature of the transport process and the differences between transport and diffusion kinetics in muscle have not been clearly described previously. We have employed the isolated, perfused rat heart as the test preparation. The process of glucose uptake by this tissue has been taken to consist of three sequential steps. These are (a) the diffusion of glucose from within the capillary to the muscle cell surface, (b) the transport of glucose through the cell membrane, and (c) the intracellular phosphorylation of the sugar. The kinetics of each of these steps has been investigated, and the extent to which each step limits, or controls, uptake has been evaluated. The effects of insulin and anoxia on uptake as a whole and on each step individually have been determined. The present study deals with heart muscle from normal rats and the following paper with muscle from diabetic rats. The use and properties of the isolated heart preparation are described in detail. Preliminary reports of some of this work have appeared earlier (8, 9).