Studies of Tissue Permeability: VI. THE PENETRATION AND PHOSPHORYLATION OF 2-DEOXYGLUCOSE IN THE DIAPHRAGM OF DIABETIC RATS

Abstract

The utilization of glucose by striated muscle of the diabetic animal is markedly impaired. Whether this is a consequence of decreased cellular permeability to glucose or a diminution in the ability of muscle to phosphorylate glucose has not been resolved, since previous investigations have been concerned with measurements of utilization rates, a parameter which does not enable one to distinguish between transport and subsequent phosphorylation. Recent observations on intact animals (1) suggested that both processes are impaired in the diabetic state. A further exploration of this problem has been carried out in vitro with an intact rat diaphragm preparation with the glucose analogue 2-deosyglucose. This sugar is phosphorylated by hexokinase as rapidly as is glucose,’ but the phosphorylated product, 2-deoxyglucose g-phosphate, is not acted upon appreciably by other muscle enzymes and hence accumulates within the cell. These properties permitted the investigation of cellular penetration and phosphorylation as separate events. In the present paper it will be shown that there is a disturbance of both penetration and phosphorylation in diabetic muscle. The former is caused by a lack of insulin, whereas the latter can be attributed, at least in part, to the action of adrenal cortical secretions. Additional observations are recorded which indicate that the cut hemidiaphragm preparation is much more permeable to sugars than the intact preparation.*