34 The Chemistry of the Injured Cell 



phate though the change of fructose to glucose is not affected (Cher- 

 nick and Chaikoff, 1951) . The other concerns the incorporation of 

 two carbon compounds into fatty acids. Insulin administration 

 overcomes both blocks. Insulin is also thought to be a factor in the 

 transport of glucose phosphate across the cell membrane, while it is 

 known to decrease the output of glucose from the liver. Excess 

 gluconeogenesis from fat in the liver has also been offered as the 

 explanation of the glycogenic infiltration in that organ (Vallance- 

 Owen, 1952) and different types of diabetes have been suggested, 

 but the position requires further investigation, especially because 

 of the interrelationships that exist between carbohydrate metabol- 

 ism and endocrine function. One intriguing example of glycogen 

 accumulation occurs in rats given 2:4-dinitrophenol subcutane- 

 ously for twenty days. The liver then recalls a glycogen storage 

 disease. It shows decreased acid and alkaline phosphatase, un- 

 changed glucose-6-phosphatase and phosphoglucomutase, and is 

 thought to result from decreased peripheral glucose utilisation as 

 happens with adrenocortical hormones (Fonnescu and Severi, 

 1955) . 



Reduced glycogen content or its complete loss is a well known 

 happening in damaged cells. A poor oxygen supply, infection or 

 intoxication are the most potent factors that bring this about, apart 

 from inanition. Most of our information comes from histological 

 observation, however, and little reliable quantitative information is 

 available. When the coronary artery is occluded glycogen disappears 

 from the heart muscle fibres in a few minutes long before there is 

 impairment of muscle capacity and cell death (Caulfield and 

 Klionsky, 1959) . This effect is very similar to that resulting from 

 autolysis or systemic anoxia (Merrick and Myers, 1954) . So, too, 

 limb ischaemia results in a fall in its muscle glycogen level, but 

 there may be a rise at the same time in liver and breast glycogen, 

 followed later by a fall (Stoner, 1958) . Repeated haemorrhage de- 

 pletes the liver of glycogen (Devos, 1952) . Needle biopsy has 

 brought convincing evidence of glycogen depletion in the liver 

 during infective hepatitis and many forms of infection. Experi- 

 mentalists, too, have shown how rapidly glycogen disappears from 

 the liver and other organs in the presence of carcinogenic dyes, 



